Category: Vaccine

Carolina Reid getting her blood drawn as part of a clinical trial for new experimental malaria vaccine based upon live malaria parasites. Carolina Reid hide caption

Carolina Reid getting her blood drawn as part of a clinical trial for new experimental malaria vaccine based upon live malaria parasites.

One Seattle morning, Carolina Reid sat in a room with nine other volunteers, each waiting to take part in a clinical trial for a new, experimental malaria vaccine.

Reid's turn came. She put her arm over a cardboard box filled with 200 mosquitoes and covered with a mesh that keeps them in but still lets them bite. "Literally a Chinese food takeout container" is how she remembers it. A scientist then covered her arm with a black cloth, because mosquitoes like to bite at night.

Then the feeding frenzy began.

"My whole forearm swelled and blistered," says Reid. "My family was laughing, asking like, 'why are you subjecting yourself to this?'" And she didn't just do it once. She did it five times.

You may be thinking this is a joke, right?

Reid's arm swelling after being bitten by 200 mosquitoes at once in order to be dosed with the experimental malaria vaccine. Carolina Reid hide caption

Reid's arm swelling after being bitten by 200 mosquitoes at once in order to be dosed with the experimental malaria vaccine.

But it's not. "We use the mosquitoes like they're 1,000 small flying syringes," explains University of Washington, Seattle physician and scientist Dr. Sean Murphy, lead author on a paper in Science Translational Medicine released on August 24 detailing the vaccine trials.

The insects deliver live malaria-causing Plasmodium parasites that have been genetically modified to not get people sick. The body still makes antibodies against the weakened parasite so it's prepared to fight the real thing.

To be clear, Murphy's not planning to use mosquitoes to vaccinate millions of people. Mosquitoes have been used to deliver malaria vaccines for clinical trials in the past, but it's not common.

Sean Murphy, lead author of a new malaria vaccine study, demonstrates how participants got their dose: by placing an arm over a mesh-covered container filled with 200 mosquitoes whose bites delivered genetically modified malaria parasites. Annette M Seilie hide caption

Sean Murphy, lead author of a new malaria vaccine study, demonstrates how participants got their dose: by placing an arm over a mesh-covered container filled with 200 mosquitoes whose bites delivered genetically modified malaria parasites.

He and his colleagues went this route because it is costly and time consuming to develop a formulation of a parasite that can be delivered with a needle. The parasites mature inside mosquitoes so at this proof of concept stage as early stage trials are called it makes sense to use them for delivery.

"They went old school with this one," says Dr. Kirsten Lyke, a physician and vaccine researcher at the University of Maryland School of Medicine who was not involved in the study. "All things old become new again."

She calls the use of a genetically modified live parasite "a total game changer" for vaccine development.

This type of vaccine is of course not yet ready for prime time. But the small trial of 26 participants did show that the modified parasites protected some participants from a malaria infection for a few months.

Murphy believes this approach could someday result in a vaccine that's substantially more effective than the world's first malaria vaccine, the RTS,S vaccine from drugmaker GlaxoSmithKline. The World Health Organization approved it last year, but it only has an efficacy rate of 30-40%.

Reid was looking for work when she joined the trial in 2018. "The first thing that caught my eye was the money," she says a $4,100 payment for participants. But when she spoke to friends who'd contracted malaria, she found a different motivation. She said it was no longer about the money at that point though it was still nice but instead being a part of important research.

A colored microscope image of the malaria parasite, Plasmodium sp. (green), infecting a red blood cell (red). Malaria is spread from infected Anopheles mosquitoes to people. The parasites infect the liver, then move into the blood. Dr. Tony Brain/Science Source hide caption

A colored microscope image of the malaria parasite, Plasmodium sp. (green), infecting a red blood cell (red). Malaria is spread from infected Anopheles mosquitoes to people. The parasites infect the liver, then move into the blood.

Malaria parasites live in the salivary glands of Anopheles mosquitoes. The disease is most common in Africa where the warm climate suits the growth of the parasite. People get malaria from the bite of an infected mosquito. Infected people can pass the malaria parasite to mosquitoes who bite them, and the cycle of infection continues.

Countries try to curb malaria with mosquito netting, insecticidal sprays, anti-malarial drugs and even by releasing genetically modified mosquitoes that can't bite or lay eggs.

Even with those measures, scientists estimate there are over 240 million cases of malaria a year and over 600,000 deaths which is why vaccines are needed.

The reason Murphy thinks this experimental vaccine should stimulate a more powerful immune response than the WHO-approved RTS,S vaccine is that it uses a whole weakened parasite. RTS,S targets "just one out of more than 5,000 proteins" the parasite produces, he says.

Others have attempted to make a malaria vaccine from disarmed parasites. What's new is that this team did the disarming with CRISPR a highly advanced pair of molecular scissors that can cut DNA.

To test how well the approach worked, Reid and the other participants had to get another round of mosquito bites this time containing the real malaria parasite.

Out of 14 participants who were exposed to malaria, seven of them including Reid came down with the disease, meaning the vaccine was only 50% effective. For the other seven, protection didn't last more than a few months.

"I actually cried when they told me I had malaria because I developed such a close relationship with the nurses," Reid says. She wanted to continue through the trials, but her infection made her ineligible. She was given a drug to clear her case of malaria and sent home.

"We think we can obviously do better," says Stefan Kappe, an author of the study and parasitologist at University of Washington Seattle and Seattle Children's Research Institute. He and Murphy hope to improve the efficacy of their team's vaccine by putting it into syringes instead of using mosquitoes so they can get the dosage right. A higher initial dose could lead to greater protection for a longer period of time.

Lyke says some scientists think using a slightly more mature version of the parasite than the one in this vaccine could give the body more time to prepare an immune response. The team is already working on that approach, says Kappe.

If future trials are promising, there are other questions to ponder. For starters: How much would this type of vaccine cost? The scientists are partnering with a small company called Sanaria to produce the modified parasites. Kappe says that increasing production capability to scale up manufacturing will require investment.

As for Reid, her experience was so positive that she went on to participate in clinical trials for a bird flu vaccine and the Moderna COVID-19 vaccine. She says that she will continue to enroll in vaccine clinical trials "for the rest of my life actually."

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Why mosquitoes were the vaccinators in a new malaria vaccine trial : Goats and Soda - NPR

The UK Health Security Agency (UKHSA) has announced that second doses of the smallpox (Jynneos) vaccine will be offered to people at highest risk from monkeypox, in order to maximise protection against the virus.

This targeted approach is also supported by modelling published in todays technical briefing 8 which suggests vaccinating 25% of the groups most at risk could significantly reduce the risk of transmission.

Whilst sexual health clinics will continue to prioritise offering first doses to those at highest risk, some clinics will also begin to offer eligible people a second dose to provide longer term protection.

The Joint Committee on Vaccination and Immunisation (JCVI) has endorsed UKHSAs proposal to offer second doses to those at highest risk, while continuing efforts to maximise uptake of the first dose within this group.

There are no current plans to widen the offer of vaccination beyond the existing priority cohorts, though this decision will be kept under review.

The NHS will call forward those that are eligible for vaccination. Second doses will be offered from around 2 to 3 months after the first dose to maximise protection.

As of 20 September, more than 45,000 people have received a dose of the vaccine including over 40,000 gay, bisexual and other men who have sex with men who are at highest risk of exposure.

In order to maximise the number of people that can be vaccinated, more clinics will offer the vaccine using intradermal administration in the coming weeks. This safe and clinically approved approach has been positively received by patients and staff where it has been used already.

UKHSA has confirmed delivery of 20,000 additional vaccines from Bavarian Nordic, the single global supplier of the vaccine being used in response to the current outbreak of monkeypox in the UK. The vaccines are available for NHS services to order and are being distributed now, with a further 80,000 vaccines expected to arrive later this month. The use of intradermal administration will mean that everyone at highest risk will have access to two doses of monkeypox vaccine in the coming months.

As of 16 September, there are 3,585 confirmed and highly probable cases of monkeypox in the UK. Following a clear peak of more than 60 cases per day in mid-July, the number of cases has decreased throughout August and continues to fall, with less than 15 cases per day on average in early September.

Analysis of wider infection trends suggests changes in behaviour in the groups most at risk may have contributed to the reduced case rates.

Dr Gayatri Amirthalingam, Deputy Director, Public Health Programmes at UKHSA said:

Its encouraging that were continuing to see fewer cases of monkeypox reported in the UK and we are grateful to everyone who has followed advice about potential symptoms, isolated as part of this outbreak or come forward for a vaccination to help limit transmission.

Prioritising vaccine stock where possible for second doses for those at highest risk will help us maximise protection and interrupt transmission. When you are called forward for vaccination, please take up the offer.

Professor Sir Andrew Pollard, chair of the JCVI, said:

The JCVI has endorsed the UKHSAs proposal that vaccination to protect against monkeypox should continue to be prioritised for those at highest risk of exposure to the virus, including offering second doses to individuals once they become eligible.

This approach will ensure the globally-limited supplies are used most effectively, continuing to break chains of transmission, as well as providing those at highest risk of exposure with longer-lasting protection.

The use of the intradermal vaccination method at some clinics also means more doses can be drawn from the vials, helping to maximise the reach of the UKs supplies and ensure second doses for all those eligible. The JCVI will keep the offer of monkeypox vaccination under review to ensure it continues to have the maximum impact on the current outbreak.

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Second vaccine doses to be offered to those at highest risk from monkeypox - GOV.UK

A structural comparison of two antibodies targeting domain 3 of Pfs48/45

The two antibodies which have the highest transmission-blocking activity, 32F3 and 85RF45.1, both bind to the C-terminal domain of Pfs48/458,12. However, these two antibodies show substantial differences in transmission-blocking activity, with 85RF45.1 completely preventing transmission at 14g/ml, while 32F3 is only ~40% effective at 70g/ml12. To rationalise these differences, and to guide future vaccine design, we determined the structure of the C-terminal 6-cys domain of Pfs48/45 bound to 32F3 (Fig.1A, Supplementary Table1). We prepared Fab fragments from 32F3, combined these with the Pfs48/45 C-terminal domain and conducted crystallisation trials. Crystals formed and a complete dataset was collected to 1.9 resolution, allowing structure determination by molecular replacement.

A The structure of the C-terminal domain of Pfs48/45 (Pfs48/45-D3; blue) bound to antibody 32F3 (orange). The upper right inset shows a close-up of a Pfs48/45 loop which becomes ordered on 32F3 binding. The lower inset shows the equivalent view of the complex of Pfs48/45-D3 (blue) bound to 85RF45.1 (red). B An alignment of the structures of 32F3 (orange) and 85RF45.1 (red) bound to Pfs48/45-D3 (blue). C Surface plasmon resonance analysis of the binding of Pfs48/45-D3 to immobilised 32F3 and 85RF45.1. In both cases, the black lines show the responses due to a two-fold dilution series with a top concentration of 7.8nM for 85RF45.1 and 125nM for 32F3. The red dashed lines show fitting to a 1-to-1 binding model.

The structure of the C-terminal domain of Pfs48/45 was largely unchanged in conformation from that observed in complex with 85RF45.1, with a root mean square deviation of 0.66 (Fig.1A, B)12,29. The most substantial change was in the loop comprising residues 357369. This loop is disordered when bound to antibody 85RF45.1 but becomes ordered through interactions with 32F3 (Fig.1A). While antibodies 32F3 and 85RF45.1 bind to overlapping epitopes, many of the contacts are not shared and the Fabs approach Pfs48/45 at different angles.

We also determined the binding kinetics for both 85RF45.1 and 32F3 to Pfs48/45, using surface plasmon resonance measurements (Fig.1C, Supplementary Fig.1). We first captured 85RF45.1 and 32F3 on different flow paths of a chip coated with protein A/G and flowed two-fold dilution series of Pfs48/45 over these antibody-coupled surfaces. Both antibodies bound to Pfs48/45 with similar affinities in the low nanomolar range (2.5nM for 85RF45.1 and 5.2nM for 32F3). However, binding kinetics differed, with 85RF45.1 showing faster association- and dissociation-rates, while 32F3 binds more slowly but forms a more stable complex. It seems likely that the slower binding kinetics of 32F3 may be due to the need for loop 357369 to become ordered on binding, while antibody 85RF45.1 has an epitope which is unchanged in structure on antibody binding, allowing faster binding kinetics.

We next aimed to determine the structure of the complete Pfs48/45 molecule, allowing us to reveal the architecture of this three-domain protein and the locations of antibody epitopes outside the C-terminal domain. Insect cell expression systems were available to produce full-length Pfs48/45 ectodomain, or to generate a protein containing the central and C-terminal domains, Pfs48/45-D2+3 [11]. Both were expressed without the GPI-anchor modification site and were purified and mixed in different combinations with one or more Fab fragments, selected from a set of antibodies which bind to different domains of Pfs48/45 (85RF45.1, 85RF45.3, 85RF45.525, 32F38, 10D8, 9D1, 7A612). Three of these complexes generated crystals: full-length Pfs48/45 bound to 10D8; full-length Pfs48/45 bound to both 10D8 and 85RF45.1; and Pfs48/45-D2+3 bound to both 10D8 and 32F3. Datasets were collected to 4.2, 3.72 and 3.69, respectively.

We attempted to determine the structures of these complexes by molecular replacement, using the structures of the C-terminal domain bound to either 32F3 or 85RF45.1 Fab as search models. In each case, the resultant electron density maps were sufficiently detailed to allow us to build a model for the central domain of Pfs48/45. This domain contains the epitope for 10D8, also allowing us to build a model for the 10D8 Fab (Fig.2, Supplementary Tables1 and 2). However, while electron density could be observed for the N-terminal domain of Pfs48/45, this region was not sufficiently well resolved to allow a model to be built.

Structures of Pfs48/45 bound to different combinations of Fab fragments or scFvs. Pfs48/45 is shown with the three domains in different shades of blue. The N-terminal domain is light blue, the central domain is mid-blue and the C-terminal domain is dark blue. 10D8 is yellow, 85RF45.1 is red and 32F3 and its scFv are orange. Each figure also shows the electron density in pale blue, shown at a contour threshold of 1.0.

The hinge between the variable and constant domains of Fabs is flexible. In case this flexibility reduced the degree of order within the crystals, we also generated scFv constructs for 85RF45.1, 32F3 and 10D8. These were purified, mixed with full-length Pfs48/45 and complexes were subjected to crystallisation trials. Crystals formed for the complex containing 32F3 scFv and a dataset was collected to 2.13 resolution, allowing structure determination by molecular replacement. This higher resolution data allowed us to build an improved model for the central domain of Pfs48/45 (Fig.2). However, the density for the N-terminal domain was still too poorly resolved to allow building of a complete molecular model of this domain. Analysis of packing within the different crystals suggested that, in each case, the N-terminal domain lies within a substantial cavity within the crystal lattice, and the lack of packing against other regions of Pfs48/45 contributed to disorder of this domain, even within a well-ordered lattice.

Recent improvements in protein structure prediction from AlphaFold230 provided a solution, allowing us to interpret the electron density maps for the N-terminal domain. AlphaFold2 correctly predicted the architecture of the central and C-terminal domains (with root mean square deviation of 1.26 for the central domain and 0.43 for the core 753/1044 atoms of the C-terminal domain), albeit with differences in loop structure (accession code Q8I6T1 at alphafold.ebi.ac.uk) (Supplementary Fig.2). We therefore compared the AlphaFold2 model for the N-terminal domain with the electron density for this domain within the three different maps. The most complete electron density for this region of Pfs48/45 was obtained from crystals of full-length Pfs48/45 bound to 10D8. The AlphaFold2 model was therefore docked as single rigid body into this electron density and was rebuilt to fit the density. This generated a model for 122 residues of the 150 residue-long N-terminal domain, with a root mean square deviation of 1.63 from the AlphaFold2 model. The N-terminus and loops 6268 and 163168 were unresolved. This model was then used to guide building of the observed portions of the N-terminal domain in full-length Pfs48/45 bound to 10D8 and 85RF45.1 (95 residues were built) and Pfs48/45-D2+3 bound to both 10D8 and 32F3 (20 residues were built). Through this approach, we generated the first molecular models of full-length Pfs48/45 derived from experimental crystallographic data, with an AlphaFold2 model used to guide building of the N-terminal domain (Fig.2, Supplementary Tables13).

We next used our structures, together with molecular dynamics simulations, to understand the organisation of Pfs48/45. Our three structures of Pfs48/45 all reveal a flattened, disc-like architecture (Fig.3A), with a 20 residue long linker before the GPI anchor. This membrane-attachment site emerges from a flat surface of the molecule, suggesting that the disc may lie, on average, parallel to the membrane, with all three domains equally exposed at the gametocyte surface.

A The structure of Pfs48/45 taken from that of full-length Pfs48/45 bound to 10D8, viewed from two different directions. The N-terminal (D1), central (D2) and C-terminal domains (D3) are light, medium and dark blue. The right-hand panel also indicates the membrane and the 20 residue long linker not included in our constructs. B Comparison of the three full-length Pfs48/45 structures. Three structures were constructed by taking the models of Pfs48/45 from the three different crystal structures of Pfs48/45 bound to different antibody combinations and aligning the structure of the N-terminal domain onto the fragments of the domain built into the electron density. These composite structures have been aligned based on the central and C-terminal domains, showing the motion of the N-terminal domain, highlighted by the red arrow. C Histogram showing the observed interdomain angles in full-length Pfs48/45 during atomistic molecular dynamics simulations. To define these angles two lines were drawn, linking the centres of mass of the N-terminal and central domains and those of the central and C-terminal domains. The angle shown is that between these lines. The three coloured histograms refer to outcomes of three independent simulations which started with the models in panel (B) with histograms being constructed by pooling five replicates for each starting structure. The black histogram is the pooled distribution of all replicates in all three starting models. D The average angle observed in the simulations from (C). is shown top-centre with the most closed observed model bottom-left and the most open model bottom-right. Red lines are as described in C. E shows the fitting of models from the molecular dynamic simulations to data from small angle X-ray scattering. Each point represents a different model and the 2 gives the quality of fit to the scattering curve. Horizontal lines show the 2 for the fit corresponding to interdomain angles found in the three crystal structures, as seen in B.

The availability of three structures of Pfs48/45 allowed us to assess its degree of flexibility within crystals. We docked the most complete model of the N-terminal domain, from the structure of full-length Pfs48/45 bound to 10D8, onto the fragments of the domain observed in the two other crystal forms and the three resultant models for the full Pfs48/45 ectodomain were aligned (Fig.3B). While the relative positions of the central and C-terminal domains were largely unchanged across these molecules, the position of the N-terminal domain changed, due to flexibility in the linker joining the N-terminal and central domains. Through these movements, the separation between the N- and C-terminal domains varied.

To further assess the degree of motion within Pfs48/45, we used molecular dynamics simulations. Three separate simulations were run, with our three independent structures of Pfs48/45,each modified to include the aligned N-terminal domain, used as three distinct starting points. In each case, we simulated the system for 500ns with 5 repeats. Analysis of these simulations revealed motion of the N-terminal domain in excess of that seen in the three crystal structures, leading to further separation of the N- and C-terminal domains. The two peaks seen in some of the individual simulations were not observed in a pooled simulation, suggesting that each individual simulation had not converged, with pooled simulations reaching a more representative endpoint. We plotted two lines though the structure; one linking the centres of mass of the N-terminal and central domains and one linking the centres of mass of the central and C-terminal domains. The angle between these lines was used as a measure of the degree of opening of the complex. This varied from 56.4 to 114.9, with an average of 72.8 and a standard deviation of 7.3 (Fig.3C, D, Supplementary Fig.3). The major peak varied from 56.4 to 92.1, although we also observed a single instance of extreme opening to 112.7 (Supplementary Fig.3A). This compares with angles of 60.3, 63.1 and 67.5 in the three crystal structures.

To compare the fit of our molecular dynamic simulations to experimental data, we subjected Pfs48/45 to small angle X-ray scattering (Supplementary Fig.4). We then sampled the molecular dynamic simulation trajectories to generate a PDB file for every 50th frame and fitted each of these to the scattering data using FoxS31 thereby generating a 2 which allows us to quantify the fit. For comparison, we also fit the input models used for simulations, with domain positions matching those found in the three crystals. We then plotted the 2 against the interdomain angle (Fig.3E). This analysis shows that no single angle fits most closely to the SAXS data, with a broad range of models, with interdomain angle 56 from 93, all fitting with a lower 2 than any of the crystal structures. Indeed 66% of the models derived from simulation fitted the SAXS scattering data more closely than the three crystal structures. This confirms that Pfs48/45 in solution is a dynamic molecule, sampling a wide range of interdomain angles, through movement of the N-terminal domain relative to the central and C-terminal domains. This flexibility may allow Pfs48/45 to adopt different conformations on binding to partners, such as Pfs230 and will also leave all three domains exposed to antibody recognition.

We next combined crystallography, electron microscopy and molecular dynamics simulations to assess how different monoclonal antibodies bind to Pfs48/45. In addition to visualising antibodies 32F3 and 85RF45.1 (Fig.1), our crystal structures revealed the epitope for 10D8 (Fig.2), an antibody with weak transmission-reducing potential which binds to the central domain of Pfs48/4512. We combined the structure of Pfs48/45 bound to 10D8 with those of the C-terminal domain bound to 32F3 and 85RF45.1 to generate a composite model, showing the structure of Pfs48/45 bound to these three antibodies (Fig.4A).

A The structure of Pfs48/45 bound to 10D8 is used as a template, and combined with structures of the D3 domain of Pfs48/45 bound to either 85RF45.1 or 32F3 to generate a model, showing the relative locations of the three antibody epitopes. B A measure of the flexibility of the residues which form the epitopes for 32F3, 85RF45.1 and 10D8, as derived from molecular dynamics simulations. Each epitope was analysed in all 15 replicates and significance levels are based on a two-sided MannWhitney U tests where *** indicates p<0.0005 and **** indicates p<0.00005. The box bounds are interquartile ranges, and the lines within boxes are the median values. Whiskers extend to 1.5-fold the interquartile range. For 32F3 vs 85RF45.1 p=0.00008; for 32F3 vs 10D8 p=0.00031; for 10D8 vs 85RF45.1 p=0.58974. C A composite model, derived from negative-stain electron microscopy structures. In each case, the complexes contained Pfs48/45 bound to 85RF45.1, together with either 9A6, 3H6, 10D8, 1F10 and 6A10. These were imaged by negative stain electron microscopy, and models were fitting into the resultant envelopes. These models were used to align the envelopes, allowing us to derive a composite model, showing the location for the five epitopes.

To understand the degree of flexibility of these three epitopes we analysed the molecular dynamics simulations presented in Fig.3, specifically assessing the motion of residues directly in contact with each of the three antibodies. This revealed that the epitope for 32F3 is significantly more flexible than those for 85RF45.1 and 10D8 (Fig.4B), predominantly due to motion of the 357369 loop, which becomes ordered on 32F3 binding due to direct interactions with the antibody (Supplementary Fig.3). This indicates that the slower association-rate for 32F3, compared to the association rates for either 85RF45.1 or 10D8, is due to this flexibility and to the need for the epitope to adopt the correct structure on antibody binding. In contrast, off-rate is likely to be determined by the degree of complementarity of the epitope and paratope when forming an interaction. Indeed, 32F3 has the slowest off-rate (Supplementary Fig.1), which correlates with a larger buried surface area for the epitope (11072 for 32F3, 8752 for 85RF45.1 and 7152 for 10D8) and a greater number of direct interactions (Supplementary Fig.3)12.

Finally, we used negative stain electron microscopy to visualise the approximate location on Pfs48/45 of the epitopes of four more antibodies. 1F10 and 6A10 are in the same competition group on the central domain as 10D8 while 9A6 is in a different competition group, binding to the same domain12. In contrast, 3H6 binds to the N-terminal domain. While 1F10 and 6A10 show some transmission-reducing activity, 9A6 and 3H6 do not12. In each case, we assembled complexes containing Pfs48/45, 85RF45.1 Fab and one other antibody Fab, with 85RF45.1 included to provide a clear marker which could be used to align and position each additional antibody. We then used negative stain electron microscopy to image the complexes and single particle analysis to determine a low-resolution structure. The Pfs48/45:85RF45.1 complex and an additional Fab model were then docked into these structures, taking into account to which domain the additional Fab bound to determine the organisation of the complex and the approximate location of the Fab. These five models were then aligned on Pfs48/45 and assembled together to show the locations of the five antibodies (Fig.4C, Supplementary Fig.5, Supplementary Table4). The locations of 10D8, 1F10 and 6A10, which are part of the same competition group, were superimposable. In contrast, 9A6 and 3H6 adopted different locations on Pfs48/45, with both protruding in approximately the same plane as that shared by the three domains of Pfs48/45.

These findings suggest that both accessibility and also unknown functional properties of Pfs48/45 contribute to the transmission-blocking efficacy of antibodies which target Pfs48/45. When attached to the membrane, through a C-terminal GPI anchor, we would expect the Pfs48/45 disc to be on average arranged horizontal to the membrane plane (Fig.3A). In this orientation, the epitope for 85RF45.1 will be most exposed on the membrane surface with the 32F3 epitope exposed to a lesser degree and the 10D8 epitope least accessible. This correlates with the order of transmission-blocking activity of these three antibodies, with 85RF45.1 as most potent and 10D8 as least potent. However, the epitopes for 9A6 and 3H6 emerge in the plane of Pfs48/45 and we would expect them to be more regularly exposed on the membrane surface than the epitope for 10D8, and yet they are not transmission-blocking12. It is also notable that neither 3H6 or 9A6 stain gametocytes, suggesting these epitopes to be buried in that context12. A possible explanation for this is that the region of Pfs48/45 bound by these antibodies may be occluded by its binding partners, such as Pfs230. Further studies of Pfs48/45 function are required to determine whether this is the case.

The structure of Pfs48/45 indicates that each of its three domains will be exposed on the gametocyte surface (Fig.3) and antibodies binding to each domain have been shown to stain gametocytes12. However, the most effective known transmission-blocking monoclonal antibodies bind to the C-terminal domain8,25. We therefore aimed to determine the degree to which antibodies against the N-terminal and central domains contribute to transmission-blocking activity, using a combination of immunisation and antibody depletion experiments.

We first produced protein consisting of the N-terminal and central domains of Pfs48/45 (Pfs48/45-D1+2) and used this to immunise mice. IgG was purified from these mice and the titres of antibodies targeting Pfs48/45-D1+2 were determined by end-point ELISA (Fig.5A). The transmission-blocking activity of these antibodies was then assessed using a standard membrane feeding assay. Antibodies were added to blood containing Plasmodium falciparum gametocytes, fed to mosquitos, and the number of ookinetes formed in mosquito midguts was counted. Total IgG, purified from mice immunised with either 0.1g or 1g of Pfs48/45-D1+2 was tested at a concentration of 750g/ml, causing almost complete inhibition (96 and 100% reductions resulting from 0.1g and 1g immunisations, respectively) in oocyte numbers (Fig.5B). When tested at 375 and 188g/ml, the total IgG from the 1g group also showed significant inhibition of 92 and 68%, respectively (Fig.5C). Therefore, protein immunogens containing just the N-terminal and central domains of Pfs48/45 are able to induce highly potent transmission-blocking antibodies.

AC Female CD1 mice (n=6 mice) were immunised twice with either 0.1g or 1g of Pfs48/45-D1+2, or 1g of Pfs25. Sera was collected three weeks after the final dose for analysis. A IgG titres as measured by endpoint ELISA using Pfs48/45-D1+2 as the coating antigen. Each symbol is for the serum sample from an individual mouse; lines represent the median of each group. MannWhitney two-tailed test was performed to compare the two Pfs48/45-D1+2 groups (p=0.0043). B, C Transmission-blocking efficacy of IgG induced by immunisation with Pfs48/45-D1+2. Total IgG was purified from the pooled serum of each group (3 weeks post-boost) and mixed with P. falciparum NF54 cultured gametocytes at 750g/mL (B) and in a separate experiment at 375g/mL and 83g/mL (C) and fed to A. stephensi mosquitoes (n=20 mosquitoes per test group of pooled IgG in a single feed experiment). IgG from naive mice was used as a negative control (normal mouse Ab); the transmission-blocking anti-Pfs25 mAb 4B7 was used as a positive control at a concentration of 94g/mL. Data points represent the number of oocysts in individual mosquitoes 8 days post-feeding; horizontal lines show the arithmetic mean. D, E Female CD1 mice were immunised three times with 5g of Pfs48/45-FL. Three weeks after the final dose sera were collected and total IgG purified. Total IgG was depleted of Pfs48/45-D3-targeting IgG using a column coupled with Pfs48/45-D3, resulting in Pfs48/45-D3. D Pfs48/45-D3 specific ELISA showing lack of recognition of Pfs48/45-D3 by Pfs48/45-D3. Pfs25-specific IgG (Pfs25) was included as a negative control. Data presented as mean+/standard deviation. E Transmission-blocking efficacy of total IgG from Pfs48/45-FL or Pfs48/45-D3 fed to A. stephensi mosquitoes at concentrations of 750g/mL, 250g/mL and 83g/mL (n=20 mosquitoes per test group of pooled IgG in a single feed experiment). IgG from naive mice was used as a negative control (normal mouse Ab); transmission-blocking anti-Pfs25 mAb 4B7 was used as a positive control. Data points represent the number of oocysts in individual mosquitoes; lines show the arithmetic mean (TRA, transmission reducing activity [% inhibition in mean oocyst count per mosquito]).

We next used a depletion approach to assess the contribution that antibodies which target the N-terminal and central domains of Pfs48/45 make to the transmission-blocking activity of IgG from mice immunised with full-length Pfs48/45. Total IgG from mice immunised with 5g of full-length Pfs48/45 was tested at a concentration of 750g/ml and showed 100% transmission-blocking activity (Fig.5D, E). This IgG was depleted of antibodies which bind to the C-terminal domain of Pfs48/45 using an affinity column and was tested for transmission-blocking activity (Fig.5D, E). Depletion of C-terminal domain (D3) specific antibodies from purified IgG was confirmed by ELISA, using Pfs48/45-D3 as the coating antigen, with no signal observed in the depleted IgG compared to the original un-depleted IgG (Fig.5D).

At all three total IgG concentrations tested, the sera depleted of C-terminal domain-targeting antibodies showed no significant difference to the sera prior to depletion (Fig.5E). This shows that the majority of the antibodies with transmission-blocking activity, induced through immunisation with full-length Pfs48/45, bind to either the N-terminal or central domains.

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Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies - Nature.com

Pharma giant Pfizer (PFE -1.10%) gained in prominence in the past couple of years thanks to its COVID-19 vaccine, Comirnaty. The company has generated billions in sales from this product alone, although many investors now think this tailwind will soon end, as the demand for coronavirus vaccines could drop substantially starting next year.

However, Pfizer has several tricks up its sleeve. The company is currently working on another promising vaccine that may not become nearly as successful as Comirnaty, but could generate at least $1 billion in annual sales if approved. Let's look into this program and what it could mean for Pfizer.

PFE data by YCharts.

On Sept. 14, Pfizer announced that it had started a phase 3 clinical trial for a potential mRNA-based influenza vaccine. The study will enroll 25,000 healthy adults in the U.S. Flu vaccines have been around for a while, and thousands of people are already inoculated every year. Current options do confer some degree of protection, but they're limited.

Preparing vaccines for the flu season is a long process. That's because researchers first have to identify the strains that are the most likely to be circulating during each season. Once that's done, it takes months to manufacture the vaccines. By the time the flu season comes along, it's entirely possible that the vaccines in circulation won't be a perfect match for the strains in circulation.

That's why flu vaccines only tend to be 40% to 60% effective, and sometimes even less. Meanwhile, the flu continues to be a serious health concern. It causes tens of thousands of hospitalizations and deaths every year. That's especially the case with those aged 65 and older, who are disproportionately represented among patients who suffer severe cases. In other words, despite the wide availability of vaccines against influenza, there's still a dire need.

Pfizer is aiming to develop a vaccine that would be an improvement over the current ones. As the company argues, mRNA technology could help deal with the strain-matching problem, since vaccines of this kind are much faster to manufacture. It could grant researchers more time to figure out which strains are more likely to arise during the flu season, and they could do so closer to the actual start of the dreaded period when influenza is most likely to be transmitted. Better strain-matching could lead to more effective vaccines against the flu and fewer hospitalizations and deaths.

Besides the fact that Pfizer's candidate could fail to prove effective in this late-stage study, it's worth noting that the company faces competition. Other companies have also highlighted the need to develop newer, more effective vaccines against the flu and are taking the mRNA approach. One of them is Moderna (MRNA -0.55%).

Moderna started a phase 3 study for its mRNA-based influenza vaccine, mRNA-1010, in June. The biotech does also have a few other candidates that target the flu that are still in the early stages of development. Those include mRNA-1073, a potential combined influenza and COVID-19 vaccine.

Moderna started its pivotal study for mRNA flu vaccines about three months before Pfizer's. But that's not what matters the most: Some of the biotechs that seemed to be in the lead in the race to develop a COVID-19 vaccine ended up losing the race. Inovio Pharmaceuticals is an excellent example.

Ultimately, the safety and efficacy of Pfizer's and Moderna's candidates will determine whether they can make a dent in the flu vaccine market -- which, according to some estimates, will be worth $12.3 billion by 2028, recording a compound annual growth rate of 7.4% through then.

It's too early to tell whether Pfizer's flu vaccines can help the company achieve its goals. Thankfully, there are other excellent reasons to invest in the pharma giant. Pfizer has generated tens of billions thanks to Comirnaty, which will allow it to expand its lineup, in part via acquisitions. That should help Pfizer set up a solid foundation for long-term growth.

Furthermore, the company currently trades at a reasonable valuation. Pfizer's forward price-to-earnings ratio is currently an attractive 7.1, compared to the pharmaceutical industry's average of 12.5. Flu vaccine or not, Pfizer looks like an excellent stock to buy and hold.

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Could This Be Pfizer's Next Billion-Dollar Vaccine? - The Motley Fool

A majority of young Americans who suffered heart inflammation after receiving a COVID-19 vaccine had abnormal magnetic resonance imaging (MRI) results, according to a new study from the U.S. Centers for Disease Control and Prevention (CDC).

CDC researchers have been following youth who experienced myocarditis, a form of heart inflammation, after receipt of the Pfizer or Moderna COVID-19 vaccines, both of which utilize messenger RNA (mRNA) technology.

Researchers reported in The Lancet on results from surveys filled out by the young Americans and their health care providers. They included results from 47 percent of the 836 patients aged 12 to 29 who experienced myocarditis after vaccination at least 90 days prior to the health care provider filling out the survey. The myocarditis for each patient was reported to the Vaccine Adverse Event Reporting System. Patients who filled out a survey themselves were excluded.

Some 81 percent of the included patients were considered by health care providers to be fully recovered or probably fully recovered from myocarditis. However, nearly half of the patients continued to report symptoms, including chest pain. And among the 151 patients who had follow-up cardiac MRI results, 54 percent had an abnormal finding, such as swelling and scarring.

The meaning of the cardiac MRI findings among the subset of patients who received cardiac imaging is unclear. Evidence of ongoing myocarditis on follow-up cardiac MRIs based on modified Lake Louise criteria was uncommon, the CDC researchers wrote. However, consistent with the few published case series of myocarditis after mRNA COVID-19 vaccination, we observed that nearly half of patients (71/151) with follow-up cardiac MRIs had residual late gadolinium enhancement, suggestive of myocardial scarring.

In some of the patients, initial cardiac imaging was normal but the follow-up imaging after several months was abnormal, which may indicate that the condition worsens over time.

The CDC is conducting additional follow-up on patients who were not considered recovered at least 12 months since symptom onset, to better understand their longer-term outcomes, the researchers said.

Ian Kracalik, a CDC researcher and the lead author, did not respond to emailed questions.

Dr. Anish Koka, a cardiologist in Pennsylvania, said that the study should dispel the ludicrous notion that clinical myocarditisa disease entity that comes to light when you have chest pain because cells in your heart are dyingis mild.

Koka, writing on Substack, said that many of the abnormalities detected on the MRIs are very likely related to myocarditis.

The CDC has said current evidence supports a causal link between the mRNA-based vaccines and two forms of heart inflammation, myocarditis and pericarditis.

These are very likely to be real scars. The valid, open question is what these scars mean long term. And the best answer is that we dont know, Koka said.

Reports to VAERS indicate that young people, especially young men, are at higher-than-expected risk from heart inflammation after receiving the Pfizer or Moderna shots.The highest reported rate is 78.7 per million second doses administered, for males between 16 and 17 years old, the CDC said earlier in September. Some risk-benefit analyses have concluded that the risks to healthy young people from the shots outweigh the benefits.

The researchers in the new study wrote, Despite the higher than expected occurrence of myocarditis after COVID-19 vaccination, the benefits of mRNA COVID-19 vaccines have been shown to outweigh the risk of myocarditis. They cited a CDC paper from July 2021 and a CDC paper from April.

Dr. Peter McCullough, a cardiologist in Texas, said on Twitter that the side effect risk to young persons is a strong reason for them to decline getting vaccinated as he highlighted the results from the new paper. McCullough said that hes seen youth at his practice with abnormal findings more than one year after vaccination.

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Zachary Stieber covers U.S. and world news. He is based in Maryland.

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Many Vaccinated Youth Who Suffered Heart Inflammation Had Abnormal MRI Results Months Later: CDC Study - The Epoch Times

Annapolis, Md (September, 23 2022) The Anne Arundel County Department of Health has expanded eligibility for the monkeypox vaccine, allowing vaccine distribution to anyone at high risk of infection to be vaccinated prior to exposure as supply allows. The vaccine was previously recommended only for people who had been potentially exposed to monkeypox.

Effective immediately, the expanded criteria for monkeypox vaccination will include anyone who meets any of these criteria:

Beginning Monday, September 26, 2022, the Department of Health will also begin testing eligible individuals for monkeypox. For those interested in being tested, call 410-222-7256.

The new eligibility criteria is aligned with current Centers for Disease Control and Prevention guidelines. Expanding eligibility will provide greater protection for individuals against monkeypox virus infection and reduce the risk of spread throughout the community.

The JYNNEOS vaccine is free. No one will be denied a vaccine based on race, gender, gender identity or expression, sexual orientation, religion, economic or citizenship status. People who meet the current eligibility criteria can schedule an appointment for the vaccine.

For more information on the monkeypox virus or to make a vaccine appointment, click here.

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Department of Health Expands Eligibility for the Monkeypox Vaccine - Anne Arundel County Department of Health

Attorneys for a group of former Maine health care workers who sued the state over its vaccine requirements last summer are asking a panel of judges in Boston to revive their case.

Last month, U.S. District Judge Jon Levy dismissed the groups lawsuit, which argued they have a religious right to refuse the vaccine overtheir belief that fetal stem cells from abortions were used to develop it. They also argued that the state mandate was discriminatory by allowing for medical exemptions, but not religious ones.

Levy ultimately disagreed.

Exempting individuals whose health will be threatened if they receive a COVID-19 vaccine is an essential, constituent part of a reasoned public health response to the COVID-19 pandemic. It does not express or suggest a discriminatory bias against religion, Levy wrote in his order on Aug. 18.

Attorneys have a month to file a brief to the 1st Circuit Court of Appeals in Boston, outlining their reasons for an appeal.

The plaintiffs worked for MaineHealth, Genesis Healthcare, Northern Light Eastern Maine Medical Center and MaineGeneral Health. All are named as defendants in the complaint, along with Gov. Janet Mills, Maine CDC Director Nirav Shah and Commissioner Jeanne Lambrew of the Maine Department of Health and Human Services.

Nine plaintiffs originally sued in August 2021, all anonymously.

The Portland Press Herald, Kennebec Journal, Morning Sentinel and Sun Journal filed a motion last November challenging the groups right to anonymity. The newspapers argued that the plaintiffs alleged fear of harm no longer outweighs the publics interest in open legal proceedings.

Both Levy and the 1st Circuit Court of Appeals agreed, ordering the group to file a new complaint that included their names in July.

Plaintiffs named in the dismissal document are Alicia Lowe, formerly an employee of MaineHealth; Debra Chalmers and Garth Berenyi, formerly of Genesis Health; Jennifer Barbalias, Natalie Salavarria and Adam Jones, formerly of Northern Light Eastern Maine Medical Center; and Nicole Giroux, formerly of MaineGeneral Health.

They are represented by Maine attorney Steve Whiting, and lawyers from Liberty Counsel, a conservative, religious law firm based in Florida that has participated in several lawsuits against Maine and other states over COVID-19 vaccine mandates and restrictions. Theyve also opposed safe and legal access to abortions and same-sex marriage, leading the Southern Poverty Law Center to identify the firm as a hate group.

Federal judges at every level the U.S. District Court,the 1st U.S. Circuit Court of Appeals in Boston andthe U.S. Supreme Court refused to block Maines COVID-19 vaccine mandate from taking effect while the courts considered the merits of the lawsuit.

The mandate took effect in October, and major health care providers reported that most workers decided to get their shots.

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Health care workers appeal dismissal of lawsuit over Maine's vaccine mandate - Kennebec Journal and Morning Sentinel

The city Department of Education has axed another 850 teachers and classroom aides bringing the total to nearly 2,000 school employees fired for failure to comply with a vaccine mandate increasingly struck down in court.

About 1,300 DOE employees who took a years unpaid leave with benefits agreed to show proof of COVID vaccination by Sept. 5 or be deemed to have voluntarily resigned.

Of those staffers, 450 got a shot by the deadline and are returning to their prior schools or work locations, DOE officials told The Post. They include some 225 teachers and 135 paraprofessionals.

The850 let go makes roughly 1,950 DOE staffers terminated since the vaccine mandate took effect on Oct. 29, 2021.

Rachelle Garcia, an elementary school teacher in Brooklyn for 15 years and mother of two, worked fully in person during the pandemic and never got sick, she said.

But she refused to get vaccinated, finally taking leave after the DOE denied her requests for a religious exemption.

I really put my eggs in one basket, hoping and praying that at the last minute our mayor would turn everything around in time for me togo back to work, she said.

Mayor Adams never lifted the vaccine mandate, while other cities and states are dropping such requirements due to relaxed CDC guidelines.

Im angry, Im hurt, to be cast aside like I was nothing. Because I couldnt give a proper goodbye to my students, other teachers told me they kept asking, When is Ms. Garcia coming back? That made me cry so much.

She is now applying for jobs on Long Island.

In all, NYC has fired more than 2,600 municipal workers not fully vaccinated, according to City Hall tallies.

But last week, a Manhattan judge ruled that an unvaccinated NYPD officer, one of the dozens terminated, cant be fired because the city gave no explanation of why it rejected his religious exemption request.

Additional reporting by Cayla Bamberger

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850 more unvaxxed NYC teachers, aides fired for not complying with mandate - New York Post

Express News Service

From Mahatma Gandhis views on vaccination to the use of children as a source of live vaccines, Dr Sajjan Singh Yadavs new book maps several such noteworthy moments in Indias journey to emerge as a global vaccine superpower of modern times.

Although the subject of the book is academic in nature, it is far from being a dry collection of facts and figures. The research is in-depth and the narrative is well structured and novelesque. Anecdotes complement historical events, and the angst and panic that has ravaged the country during outbreaks of epidemics such as smallpox, plague, cholera, polio and Covid-19 come through eloquently. So does the sense of triumph in making breakthroughs to find cures for these diseases, making the book read-worthy also for people beyond scholars and policymakers in the field.

Dr Yadav takes the readers back to the beginnings of the coronavirus pandemicto a tense WHO office in China on New Years Eve in 2019 after the Wuhan Municipal Health Commission detected a cluster of cases of pneumonia of an unknown naturepainting, retrospectively, a terrifying picture of a world immersed in celebrations, unaware of what awaited them.

The tale of the struggle of the researchers to trace the route of the coronavirus into the human community is told with gripping fervour. From the elusive search for patient zero to the futile efforts and impediments faced by scientists to trace the actual mode of transmission of the virus, Dr Yadav captures the various crests and troughs of Indias war against Covid-19 in a captivating manner. He explores and enlists the various theories and conspiracies around the possible ways the virus invaded the human population, including the assumption that the virus could have escaped from a laboratory or that it was part of a more sinister ploy.

Stories from a pre-vaccine India going back to the seventh century, when people practised various ways of acquiring immunity, make for an interesting read. For instance, oral consumption of snake venom was considered an effective method to deal with snake bites, a toxin immunity method that the western world discovered many centuries later.

Also discussed at length is Indias vaccine outreach programmeVaccine Maitrithat established the credibility of India as a reliable vaccine producer. Dr Yadav captures how Vaccine Maitri resulted in the western world beginning to see India as a counterbalancing force to the growing influence of China in the region and the emergence of new geopolitics. Social impediments faced during inoculation drives in India, including administrative complacency and vaccine hesitancy among people are addressed.

With peoples renewed awareness about vaccines in the aftermath of the Covid-19 pandemic, the book is certainly a topical read, and the authors background as a bureaucrat in the Ministry of Health and Family Welfare only helps.

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'India's vaccine growth story' book review: Far from being a dry collection of facts and figures - The New Indian Express

If youre like an estimated 99% of people born before 1980, chances are youve had the varicella-zoster virus, which causes chickenpox. It usually shows up in childhood with a trademark itchy and crusty rash, though it can strike at any time, with or without symptoms.

Many people who got chickenpox as a child have long since forgotten about it or perhaps never knew they had it in the first place. But fast forward a few decades and you may experience a potentially painful and long lasting complication: herpes zoster, also called shingles.

There is a shingles vaccine. The Food and Drug Administration (FDA) approved Shingrix in 2017 after finding it safe and highly effective at preventing shingles. But its mostly recommended for people ages 50 and over.

Read on to learn about the reasons behind the over-age-50 rule and a few exceptions to that rule.

The Centers for Disease Control and Prevention (CDC) recommends the shingles vaccine for people with healthy immune systems who are ages 50 and over. This is because your immune system becomes less robust as you age, so your risk of developing shingles increases.

The CDC also recommends the vaccine for people ages 19 and over who are immunocompromised. This means they have a weakened immune system.

Shingrix is a vaccine that contains an inactive form of the herpes zoster virus. It helps you develop an immunity to the active virus.

Adults receive the vaccine in two separate doses. Generally, healthy adults over age 50 get their second dose 2 to 6 months after the first dose. Immunocompromised adults may get the second dose sooner.

There is no maximum age for getting Shingrix.

Shingles is caused by a reactivation of the varicella-zoster virus, which is the virus that causes chickenpox.

When you get chickenpox and recover, the varicella-zoster virus doesnt go away. Instead, it stays dormant in your nerve cells. As you get older, your body is less able to fight off viruses. During this time, the virus can reactivate.

The hallmark sign of shingles is a pronounced rash of painful blisters filled with clear fluid. It usually shows up on one side of the body, especially on the head, neck, or torso. That said, it can appear anywhere on your body.

Other symptoms include:

The blisters typically start healing within 7 to 10 days and go away within a month. Yet the condition can sometimes cause persistent nerve pain, called postherpetic neuralgia (PHN).

PHN may affect the same area where you had the shingles rash. It can persist for months or years, become intensely painful, and sometimes interfere with daily life.

About 1 million people get shingles each year. The risk of getting shingles gets higher as you get older. In fact, people ages 65 or over are three times more likely to get shingles than younger people.

According to the CDC, 1 in 3 people will get shingles in their lifetime. Shingles is more common in women than in men, and it is more common in white people than in Black people.

Risk factors for shingles include:

Certain conditions or medications that affect your bodys immunity also increases your risk, particularly:

People born after 1995 are less likely to get shingles because they are less likely overall to get chickenpox. That year, a vaccine was released, which reduced chickenpox transmission significantly.

You can get shingles after vaccination with the chickenpox vaccine, but its less likely than if you got chickenpox.

Depending on when you get Shingrix, the vaccine is more than 90% effective in preventing shingles and PHN.

Chickenpox and shingles are caused by the same virus, varicella-zoster. When you recover from chickenpox, the virus stays in the cells in your nervous system.

It can become active again if your body is no longer able to suppress it. It spreads down nerve fibers and up to your skin, causing a rash, inflammation, burning, and pain.

A doctor will examine the rash on your skin and ask you about your symptoms. This is usually how healthcare professionals diagnose shingles.

A healthcare professional may remove some fluid from a blister for testing, but typically this is not necessary.

Vaccination is the key to preventing shingles. The CDC recommends:

According to the CDC, you should get the vaccine even if, in the past, you:

Creating and maintaining healthy lifestyle habits such as stress management, a healthy diet, regular exercise, and getting plenty of sleep can also help prevent or lessen flare-ups.

Shingles can be painful but the blisters often begin to heal within a week. Your skin usually clears up within a month.

People who develop PHN can have it for months or years afterward, but not everyone who has shingles will develop PHN.

Healthcare professionals can help treat shingles and shorten its duration with prescription antiviral drugs. These can also reduce your likelihood of having PHN.

Most people only get shingles once, though it is possible to get it again.

Shingrix is not recommended for adults under age 50 who have a healthy immune system.

It is recommended for adults ages 19 or over who are immunocompromised, such as people with an immune-related health condition or who are receiving immunosuppressive agents, which are medications that reduce the bodys immune response. These medications may help prevent organ rejection after an organ transplant and treat other medical conditions.

Its recommended that you get a second dose between 2 and 6 months after the first. But, if you have waited longer than 6 months, according to the CDC, you will not have to start over. Just get your second dose as soon as possible.

Yes. You can still catch the varicella-zoster virus if youve never had chickenpox, and that may cause shingles.

Immunity stays strong for at least 7 years and is more than 90% effective at preventing shingles and PHN among people ages 50 and over, per the CDC. It is between 68% to 91% effective in immunocompromised adults over age 18.

Most people dont develop side effects from the shingles vaccine, but some can occur. The vaccine is injected into your arm, so pain and soreness at the injection site are common.

The FDA also issued a warning in 2021 that there may an association between receiving the vaccine and developing Guillain-Barr Syndrome (GBS), though the relationship is poorly understood and more research is needed.

GBS is a rare condition in which your bodys immune system attacks part of the nervous system.

No, the CDC recommends that all people over age 50 get the shingles vaccine.

You should not get Shingrix if you:

Shingles is a painful condition caused by the same virus as chickenpox. The virus can remain dormant in your nervous system for decades before reactivating.

There is one FDA-approved vaccine that prevents shingles and its complications. Its usually given to adults over age 50 or to those ages 19 or over who have compromised immune systems. Your doctor may be able to prescribe it to you sooner depending on your circumstances.

If you do get shingles, it usually goes away within a month. Yet its possible to develop PHN that lasts for months or years. Your healthcare professional may be able to prescribe antiviral drugs that will shorten the duration of the shingles infection and help prevent PHN.

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Is There A Minimum Age for the Shingles Vaccine? - Healthline