Category: Vaccine

BOSTON and LEXINGTON, Mass., Feb. 15, 2024 /PRNewswire/ --The Defense Threat Reduction Agency's (DTRA) Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense (CBD) Program has awarded, through the Medical CBRN [Chemical, Biological, Radiological, and Nuclear] Defense Consortium (MCDC) requirement 22-05, "Adjuvant Activity to Vaccines Prototype," a 5-year contract totaling up to $31 million including program options to the team of Ginkgo Bioworks, Inc. (NYSE: DNA) and SaponiQx, Inc. (a subsidiary of Agenus Inc., NASDAQ:AGEN) to discover and develop next-generation vaccine adjuvants. Partners in adjuvant discovery and development since 2021, Ginkgo, which is building the leading platform for cell programming and biosecurity, and SaponiQx, developing a visionary adjuvant development platform, will use a combination of high-throughput empirical and artificial intelligence/machine learning approaches, including Generative Molecular Design (GMD), to develop superior novel saponin-based adjuvants.

Adjuvants are components of vaccines that help to enhance the magnitude, breadth, and duration of the immune response to vaccination. Currently, only a handful of adjuvants are available for human use in licensed vaccines. SaponiQx's STIMULON QS-21 is a key adjuvant component in market-leading vaccines for shingles, malaria, and respiratory syncytial virus. Novel adjuvants with enhanced properties, including tailored humoral and cellular immune responses, could pave the way for a new wave of innovative vaccines against existing and emerging pathogens.

"The COVID-19 pandemic revealed the critical need for safe, effective, and accessible vaccines against emerging biothreat agents," said Jennifer Wipf, SVP, Head of Commercial Cell Engineering at Ginkgo Bioworks. "Imagine a future where vaccines are not only more affordable but also provide consistent protection in fewer doses, without causing discomfort or requiring refrigeration. We're very excited by this opportunity to strengthen and expand the SaponiQxGinkgo partnership and to work with DTRA to make that future a reality."

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"Building on our achievements with STIMULON QS-21, SaponiQx is excited to realize our company's founding vision of harnessing the potential of Generative Molecular Design to dramatically increase access to lifesaving vaccines around the world," said Rebecca Kurnat, Head of Operations at SaponiQx.

The partners aim to demonstrate in the laboratory and in animal studies the ability of these novel adjuvants to protect against challenges from biothreat agents, such as the plague, and to provide lower cost, sustainable and scalable manufacturing processes by leveraging Ginkgo's leading platform for cell programming. The partners intend to design candidate adjuvants using SaponiQx's leading platform for adjuvant generation, and to identify additional candidates by screening natural extracts for previously uncharacterized saponins and creating non-natural saponins with enzyme-based techniques. Harnessing a first-of-its-kind "data lake" for adjuvants, they plan to use iterative GMD to propose and optimize adjuvant structures against eight functional parameters. Adjuvant candidates will be put through in-depth testing, first in the laboratory for immune and toxicity responses, and then in studies of their effectiveness in protecting vaccinated animals from pathogens; QS-21 and the related QS-7 will serve as benchmarks.

By leveraging Ginkgo's leading platform for cell programming, the partners also intend to develop more affordable, sustainable, and scalable adjuvant manufacturing processes. Ginkgo will develop a first-generation Adjuvant Development Candidate (ADC) production method, using a heterologous production strain such as brewers' yeast, Saccharomyces cerevisiae. Ginkgo's platform powers iterative DesignBuildTestLearn-driven cell engineering to enable the rapid prototyping, optimization, and development of proteins, enzymes, metabolic pathways, and whole organisms under commercial-scale manufacturing conditions. Development of a first-generation ADC production method could facilitate further development of a sustainable mass-production manufacturing process for these complex adjuvants.

About Ginkgo Bioworks

Ginkgo Bioworks is the leading horizontal platform for cell programming, providing flexible, end-to-end services that solve challenges for organizations across diverse markets, from food and agriculture to pharmaceuticals to industrial and specialty chemicals. Ginkgo's biosecurity and public health unit, Concentric by Ginkgo, is building global infrastructure for biosecurity to empower governments, communities, and public health leaders to prevent, detect and respond to a wide variety of biological threats. For more information, visitginkgobioworks.com andconcentricbyginkgo.com, read ourblog, or follow us on social media channels such as X (formerly known as Twitter) (@Ginkgo and @ConcentricByGBW), Instagram (@GinkgoBioworks and @ConcentricByGinkgo), Threads (@GinkgoBioworks) orLinkedIn.

About SaponiQx

Founded in 2021, SaponiQx, a subsidiary of Agenus Inc., stands at the forefront of saponin-based adjuvant discovery and manufacturing. Its mission is to provide scalable and affordable vaccine adjuvants to enhance global health. Its proprietary adjuvant, STIMULON QS-21, forms an integral part of the AS01 adjuvant used in several leading vaccines. STIMULON is a trademark of Agenus Inc., the parent company of SaponiQx Inc.

Forward-Looking Statements of Ginkgo Bioworks

This press release contains certain forward-looking statements within the meaning of the federal securities laws, including statements regarding the capabilities and potential success of Ginkgo's cell programming platform. These forward-looking statements generally are identified by the words "believe," "can," "project," "potential," "expect," "anticipate," "estimate," "intend," "strategy," "future," "opportunity," "plan," "may," "should," "will," "would," "will be," "will continue," "will likely result," and similar expressions. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including but not limited to: (i) volatility in the price of Ginkgo's securities due to a variety of factors, including changes in the competitive and highly regulated industries in which Ginkgo operates and plans to operate, variations in performance across competitors, and changes in laws and regulations affecting Ginkgo's business, (ii) the ability to implement business plans, forecasts, and other expectations, and to identify and realize additional business opportunities, (iii) the risk of downturns in demand for products using synthetic biology, (iv) the uncertainty regarding the demand for passive monitoring programs and biosecurity services, (v) changes to the biosecurity industry, including due to advancements in technology, emerging competition and evolution in industry demands, standards and regulations, (vi) our ability to realize the expected benefits of merger and acquisition transactions, (vii) the outcome of any legal proceedings against Ginkgo, including as a result of recent acquisitions, (viii) our ability to realize the expected benefits from and the success of our Foundry platform programs, (ix) our ability to successfully develop engineered cells, bioprocesses, data packages or other deliverables, and (x) the product development or commercialization success of our customers. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the "Risk Factors" section of Ginkgo's quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission (the "SEC") on November 8, 2023 and other documents filed by Ginkgo from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and Ginkgo assumes no obligation and does not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Ginkgo does not give any assurance that it will achieve its expectations.

GINKGO BIOWORKS INVESTOR CONTACT:

investors@ginkgobioworks.com

GINKGO BIOWORKS MEDIA CONTACT:

press@ginkgobioworks.com

Forward-Looking Statements of SaponiQx

This press release includes forward-looking statements, subject to risks and uncertainties, concerning the development of vaccines and adjuvants. Refer to the Risk Factors in Agenus' latest Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the SEC for a detailed discussion of these risks.

SAPONIQX MEDIA CONTACT:

communications@saponiqx.com

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SOURCE Ginkgo Bioworks

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Preparation of mRNA

The antigen was designed using the DNA sequence encoding the spike protein of the SARS-CoV-2 Omicron variant. The mRNA vaccine plasmid was produced by inserting antigen DNA into multiple cloning sites on the mRNA platform using restriction enzymes (Pac1 and Cla1), as previously described46. After the mRNA vaccine template was linearized using Not1, mRNA was produced using the EZ T7 High Yield In vitro Transcription Kit (Enzynomics, Daejeon, Korea) according to the manufacturers protocol. Capping was performed using SC101 (STPharm, Siheung, Korea), and UTP was replaced with N1-methyl-pseudouridine (Trilink, San Diego, CA, USA). Total mRNA was precipitated using lithium chloride and purified using cellulose, as described previously47.

Lipid nanoparticles (LNPs) were prepared according to a reported protocol48. Briefly, all lipid components were dissolved in ethanol at a molar ratio of 50:10:38.5:1.5 (SM-102; distearoylphosphatidylcholine cholesterol, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000), and mRNAs were dissolved in sodium citrate buffer (50mM; pH 4) solution at a charge ratio of N/P=6. LNPs were formulated using NanoAssemblr IgniteTM (Precision Nanosystems, Vancouver, Canada) by mixing aqueous and organic solutions at a ratio of 3:1 and a total flow rate of 10mL/min. The LNP solution was concentrated by ultrafiltration using an Amicon Ultracentrifugal filter (UFC9030, Merck Millipore, Billerica, MA, USA), following the manufacturers instructions.

The size and Zeta potential of the mRNA vaccine were measured using a zetasizer with diluted mRNA vaccine in water (Zetasizer Nano Zs, Malvern Panalytical, Malvern, Worcestershire, UK). The encapsulation efficiency of LNP is determined by Ribogreen assay. Both Triton X-100 treated or untreated mRNA vaccines were incubated with Ribogreen reagent of Quant-it RiboGreen RNA Assay Kit (Thermofisher, Waltham, MA, USA, Cat. R11490). A microplate reader analyzed the fluorescence for the total and free mRNA amount. The following formula was used to obtain the encapsulation efficiency of the mRNA vaccine:

$${rm{Encapsulation; efficiency}}left( % right)=left[left({rm{Total}},{rm{mRNA}}-{rm{free}},{rm{mRNA}}right)/{rm{total}},{rm{mRNA}}right]times 100 %$$

The endotoxin level is determined to be lower than 0.1 EU/ml using the LAL assay kit (Cat. L00350, Genscript, Piscataway, NJ, USA).

Three microliter of mRNA vaccine solution was loaded onto a holey carbon grid (Quantifoil R1.2/1.3, 200 mesh Cu, Structure Probe Inc., USA) treated with a glow discharger at 15mA for 60s to increase the loading efficiency. The grid was blotted for 4s at 15C with 100% humidity using a Vitrobot Mark IV (Thermofisher, USA, SNU CMCI) and immediately plunge-frozen in liquid nitrogen-cooled liquid ethane. The grids were imaged with TEM (JEM-2100F, JEOL, Japan) while maintaining the temperature at ~180C at an acceleration voltage of 200keV. Images were recorded using an ultrascan 1000 electron detector.

Female Balb/c and C57BL6 mice at the age of 68 weeks were obtained from Dae-Han Biolink Co. (Eumseong, Korea) and housed in a controlled environment (inverted 12-h daylight cycle) with free access to food and water. All procedures were complied with the ARRIVE guidelines and approved by the Institutional Animal Care and Use Committee of the Samsung Biomedical Research Institute (#2022032201). The Samsung Biomedical Research Institute is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International and abides by the Institute of Laboratory Animal Resources guidelines. Mice were fed a normal-fat diet (containing 5% fat) and simultaneously treated with LPS from Escherichia coli (Sigma, St Louis, MO, USA). The surgical procedure for inserting the osmotic pump followed the manufacturers instructions. Briefly, after the hair was shaved, the back of the mouse was incised, and a space was made in the subcutaneous tissue. The device was inserted into the space, and the incision was closed using wound clips (7mm). The mice were implanted with an osmotic pump (Alzet model 1004; DURECT Corp., Cupertino, CA, USA) filled with either Tween-saline (0.9% NaCl and 0.1% Tween 80 in distilled water, Sigma), normal saline control, or LPS diluted in Tween-saline infused at 300g/kg/day for 4 weeks (LPS group)49. For blood collection, mice were anesthetized with isoflurane (Isotroy 100, Troikaa, Gujarat, India), and blood was collected from the facial vein. At the defined endpoint (2 days after the boost), mice were euthanized by CO2 inhalation, and their spleens, lungs, blood, hearts, and muscles were harvested.

The pump-implanted animals were randomly assigned to four groups for administering the intramuscular SARS-CoV-2 mRNA vaccine or normal saline control (groups: saline pump, saline pump + mRNA vaccine, LPS pump, and LPS pump + mRNA vaccine). The mice were immunized intramuscularly with 10g of the Omicron S mRNA vaccine with the sequence encoding the spike protein from the SARS-CoV-2 Omicron variant. The mRNA expression platform has been previously described22. The immunization schedule comprised two injections: an initial prime injection followed by a booster injection, with a 2-week interval between injections. Once the immunization protocol was completed, the mice were euthanized 2 days after immunization, and whole blood samples and tissues were collected.

Splenocytes (1106) isolated from immunized mice were cultured in 96-well plates. Subsequently, the samples were treated with Brefeldin A (Golgi plug, BD Biosciences, Franklin Lakes, NY, USA) and stimulated with antigen peptides of the spike protein from the SARS-CoV-2 Omicron variant (5g/mL) in RPMI medium for 12h at 37C. Then, the splenocytes were treated with anti-mouse CD16/32 (Invitrogen, Waltham, Massachusetts, USA) for 20min at 4C. To stain surface proteins such as CD8, the splenocytes were stained with anti-mouse CD8 fluorescent antibody for 30min at 4C in the dark. Then, the samples were fixed and permeabilized using BD Cytofix/Cytoperm (BD Biosciences), stained with anti-mouse tumor necrosis factor alpha (TNF-) and granzyme B fluorescent antibody for 30min at 4C in the dark. For detecting the levels of M1 and M2 macrophages in the lungs using flow cytometry, lung tissues excised from immunized mice were digested with Hanks Balanced Salt Solution containing 1.5mg/ml collagenase A, 0.1mg/ml Dnase1 (Sigma Aldrich, Burlington, Massachusetts, United States) for 1h at 37C and stained using anti-mouse CD11b, CD11c, and F4/80 with the surface protein staining method used for splenocytes. The samples were then fixed and permeabilized using a Foxp3 Fixation Kit (Invitrogen) according to the manufacturers instructions. The cells were stained with anti-mouse CD206 CD8 fluorescent antibody in the dark for 30min at 4C. The samples were analyzed using a CytoFlex flow cytometer (Beckman Coulter, Brea, CA, USA), and data were analyzed using CytExpert (Beckman Coulter, Brea, CA, USA).

Enzyme-linked immunosorbent assays (ELISAs) were performed to assess antigen-specific total IgG levels in mouse serum. Briefly, a 96-well plate was coated with S protein from the SARS-CoV-2 Omicron variant at a concentration of 100ng/well and incubated overnight at 4C. The wells were then blocked with 100l blocking buffer (1% BSA in PBS) for 1h at room temperature. The serum samples diluted with blocking buffer (at 1:20) were added to the wells and incubated for 2h at room temperature (2022C). After the incubation period, the wells were washed thrice with 200l PBS-T (PBS containing Tween 20). Horseradish peroxidase-conjugated anti-mouse IgG antibodies (from Bethyl Laboratories, Montgomery, TX, USA) were added to the wells and then the plates were incubated at room temperature for 1h. The antibodies were appropriately diluted in blocking buffer (at 1:5000). Following three washes with PBS-T, tetramethylbenzidine substrate was added to the wells, and the plates were incubated for 15min. The reaction was stopped by adding 2N H2SO4. Finally, the optical density was measured at 450nm using a microplate reader (GloMax Explorer, Promega, Seoul, Republic of Korea).

Splenocytes (5105) isolated from immunized mice were cultured in 96-well MultiScreen-IP Filter Plates (Millipore, Burlington, MA, USA) and stimulated with antigen peptides of spike protein from the Wuhan SARS-CoV-2 strain (5g/ml) in RPMI medium for 24h at 37C. The ELISpot assay for detecting IFN- secreted from splenocytes was performed as per the manufacturers instructions (Mab-tech, Stockholm, Sweden).

The epididymal fat, liver, lung, muscle, and pancreatic tissues of osmotic pump-implanted mice were fixed in 10% neutral formalin. After fixation, the samples were embedded in paraffin and stained with hematoxylin and eosin (H&E). The percentage area of myocardial inflammation was determined using computer-assisted analysis. Two different areas of each heart were quantified using ImageJ software1.45s (NIH, MA, USA), as described previously50. To analyze the damaged muscle area, a Motic EasyScan Digital Slide Scanner (Motic Hong Kong Ltd., Hong Kong, China) was used to randomly capture 510 images of the affected regions. These images were then analyzed for the cross-sectional area (CSA) of the centrally nucleated regenerating myofibers using ImageJ software51. The procedures were performed by investigators who were blinded to the identities of the samples. In the SARS-CoV-2 spike immunohistochemistry procedure, Dako Retrieval Solution (pH 6.0, S2369) was utilized for antigen retrieval through incubation of sections. To mitigate nonspecific binding, a blocking step of 1-hour duration was carried out using Dako Protein Block Serum-Free (X0909). Subsequently, the sections were exposed to anti-SARS-CoV/SARS-CoV-2 (COVID-19) spike antibody (1:200; GTX632604, GeneTex) for 24h at 4C. The visualization of antigens was enabled using the Dako Envision Detection system Peroxidase/DAB+ (K5007). Following this, the slides were dehydrated and mounted after counterstaining with hematoxylin. Images of the SARS-CoV-2 spike protein were captured randomly using a Motic Easyscan Digital Slide Scanner (Motic Hong Kong Limited).

Total RNA was extracted from lung tissue using the TRIzol reagent (Invitrogen, Grand Island, NY, USA), and cDNA was synthesized using a cDNA synthesis kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturers instructions. Real-time PCR was performed using the SYBR Green Master Mix (Applied Biosystems, Foster City, CA, USA) to compare the mRNA levels of genes associated with inflammation, myogenesis, muscle types, and mitochondria. The primer sets were synthesized by SFC-probe (Cheongju, Korea) for inflammation-related genes and Bioneer (Daejeon, Korea) for the remaining genes. The primer sequences are listed in Supplementary Table 1.

Plasma was isolated from mouse blood and processed according to the manufacturers protocol for the Creatine Kinase Activity Assay Kit (3050 Spruce Street, St. Louis, MO, USA). The creatine kinase activity was determined by measuring absorbance (340nm) using a VICTOR Nivo TM multimode Microplate Reader (PerkinElmer, Waltham, MA, USA) following the standard procedure for assessment.

Statistical analyses were performed using Prism 8 software (GraphPad, San Diego, CA, USA). Data were presented as meanstandard deviation. Significant differences between means were determined using Students t-test, and P values less than 0.05 were considered statistically significant.

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

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Assessing the impact of mRNA vaccination in chronic inflammatory murine model | npj Vaccines - Nature.com

Rutgers University students failed to revive a lawsuit raising constitutional challenges to a school policy that required students to be vaccinated against Covid-19 before returning to campus in 2021.

The US Court of Appeals for the Third Circuit on Thursday affirmed a lower courts September 2022 dismissal of the complaint, saying that the students didnt have a fundamental constitutional right to be free from mandatory vaccinations and that Rutgers had a rational basis for adopting its vaccine policy.

The universitys decision to phase in its policy by delaying the vaccine mandate for its staff didnt violate the students equal protection ...

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Rutgers' Covid-19 Vaccine Mandate Survives Scrutiny on Appeal - Bloomberg Law

Limited data exist on the safety and efficacy of vaccines for pregnant women living with HIV (PWLWH), which can lead to difficult policy decisions for this population, according to a review published in eClinicalMedicine. PWLWH should be the focus of studies in the future, the authors conclude.

Mother-to-child transmission of HIV has been largely eliminated due to the usage of combined antiretroviral therapy (cART). The estimated 5.4 million children worldwide who are HIV-exposed but uninfected (HEU) often have vulnerability to other infections. Vaccine trials often do not include pregnant women, especially PWLWH who could benefit from the vaccines to protect their infants. This study aimed to assess the safety and efficacy of vaccines that were given to PWLWH that could reduce the morbidity and mortality of HEU.

Pregnant woman | Image credit: pressmaster - stock.adobe.com

MEDLINE, Embase, Web of Science, Virtual Health Library, and Cochrane Library were used to search for studies that involved the safety and efficacy of vaccines given to PWLWH. The search specifically looked for randomized controlled trials and observational studies that took place between the inception of the database and September 6, 2023. Studies were eligible if the study included a vaccine being given to a PWLWH during their pregnancy with a controlled group of women who were not living with HIV. Studies were excluded if they were review articles, a case series, conference abstracts, letters, or animal studies.

Data extracted from the studies included the HIV status of the mother, treatment they received, gestational age at the time of vaccine distribution, and the formulation of the vaccination that was given.

There were 12 studies included in the final analysis which included 3744 pregnant women, of which 1714 were PWLWH. The studies came from South Africa, Brazil, and Malawi. Pneumococcal, influenza, and group B streptococcus vaccines were tested in this population.

There were 5 studies that reported on the safety of the vaccines in 3456 pregnant women, of which 1250 were PWLWH. A total of 4.1% of PWLWH reported at least 1 severe local reaction and 18.6% reported at least 1 severe systemic reaction in 1 of the studies. This is compared with pregnant women without HIV, who reported at least 1 severe local reaction in 5% of cases and at least 1 severe systematic reaction in 15% of cases. An increased rate of injection site reactions were reported in a separate study. The most common severe adverse event was preterm births, which occurred in 17% of PWLWH compared with 10% of pregnant women without HIV.

Antibodies in PWLWH from vaccines were found to be lower compared with pregnant women without HIV after 4 weeks, even though the antibodies increased in PWLWH from baseline. The pooled mean difference in the concentration of antibodies from before the vaccination to 28 to 35 days after found that there was an increase in the concentration of antibodies in the 3 studies that did the analysis. However, when comparing PWLWH to pregnant women without HIV, the latter were found to have significantly higher antibody concentration compared with PWLWH (mean difference, 141.8; 95% CI, 194.9 to 88.6).

There were some limitations to this study. The PWLWH who were included in this study make up a small percentage of the overall population of PWLWH. The methodological quality of the studies was important to the findings. The results of only 3 studies were able to be pooled for the meta-analysis. None of the studies used in the review used the Global Alignment of immunization criteria to measure the safety of vaccines.

The researchers concluded that more data on vaccine safety in pregnant women is necessary for any new vaccines coming to the market. The availability of uniform accurate data and standardized definitions will improve maternal vaccine confidence especially in special sub-populations such as PWLWH who may require different vaccine formulations or schedules to keep themselves and their infants protected, the authors wrote.

Reference

Nakabembe E, Cooper J, Amaral K, et al. The safety and immunogenicity of vaccines administered to pregnant women living with HIV: a systematic review and meta-analysis. eClinicalMedicine. 2024;69:102448. doi:10.1016/j.eclinm.2024.102448

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Vaccine Confidence in Pregnant Women Living With HIV Requires Further Study - AJMC.com Managed Markets Network

Getting vaccines from manufacturing sites into people's arms is a complex process even in normal conditions. During the biggest pandemic in 100 years, these challenges become magnified, which meant COVAX also had to adapt to ensure the billions of vaccines it procured on behalf of countries across the world could be delivered quickly and effectively.

To mark the publication of Gavi's newanalysis paperon this delivery effort, here are five of the key factors that helped achieve one of the largest global vaccination campaigns ever attempted.

In low- and middle-income countries, one of the hurdles affecting vaccination programmes is inability to ensure a "cold chain", which is where vaccines are stored at low temperatures from the moment shipment arrives to the time they are injected into someone's arm. Unstable electricity supplies or inadequate health system infrastructure can risk vaccines being stored at incorrect temperatures, which can render them useless.

Like many other vaccines, COVID-19 vaccines were distributed by plane, truck, motorcycle and in the most remote places, by foot. The challenge was that the first COVID-19 vaccines needed not just standard vaccine cold storage temperatures of 28C but ultra-cold storage at between -90C and -60C.

During the pandemic, 73 lower-income countries received support to increase their cold and ultra-cold chain. COVAX's response was the largest deployment of ultra-cold chain equipment in history. Although Gavi had supported the installation of cold-chain equipment previously, this new initiative was complex for various reasons. Ultra-cold chain equipment is more complicated to install and requires specialist training to maintain. Moreover, shipping and installation was happening at a time when most of the world had shut down to stop COVID-19 spreading.

Despite these hurdles, COVAX financed, coordinated and delivered 948 ultra-cold chain freezers to nearly 70 countries during 2021 and 2022.

Getting vaccines to those who need them requires an extraordinary amount of logistical planning, which can be challenging in an unfolding pandemic when countries aren't sure how many doses they will need, and may not have the infrastructure to deliver doses even when they do receive them. Sometimes, doses end up being wasted through poor planning or unexpectedly low uptake.

In late April 2021, the Democratic Republic of the Congo (DRC) handed over half a million doses of COVID-19 vaccines that they had received from COVAX the previous month. Those half a million doses were part of a consignment of 1.3 million doses redeployed to other African nations: Angola, Central African Republic, Ghana, Madagascar and Togo.

The DRC government knew it would be unable to administer them before their expiry date, and so it alerted COVAX knowing that the vaccines would be used to protect people elsewhere, and that it could receive its allocation at a later date when it was able to deliver them to people.

Redistribution of doses is not always this smooth, as countries can sometimes hold on to vaccines till they are expired and it's too late to give them away. On the back of this experience, COVAX developed a vaccine redeployment policy, launched in 2021 when supplies of doses were still stretched thin, to support countries wanting to ensure doses they could not use did not go to waste. Almost 2million doses were redeployed in this way. COVAX worked with the African Union to ensure that dose donations were only accepted once a country was ready to take them on.

COVAX was designed to reduce vaccine inequity, and by January 2022, although more than 12 billion doses of COVID-19 vaccines had been delivered worldwide from all sources, it was clear that inequity was still rampant low-income countries (LICs) had only received 0.2 billion doses, a shocking 1.6% of the number of doses delivered. At that time, only 13% of people in LICs had been fully vaccinated with a primary series of two doses, compared to 60% of the global population.

The reasons varied from operational challenges to a lack of health care workers, issues in accessing vaccines, and demand issues, such as a lack of information, vaccine hesitancy and COVID-19 misinformation. To address this inequity, Gavi, WHO and UNICEF created the COVID-19 Vaccine Delivery Partnership (CoVDP) in January 2022 to provide focused support to the 34 countries that were at or below 10% primary series coverage at this time.

CoVDP focused especially on country engagement, demand planning, providing operational funding, delivery coordination and reaching high-priority groups: health care and other frontline workers, older adults and those livingwithcomorbidities.

By June 2023, just six countries had primary series vaccine coverage below 10%, compared to 34 in January 2022. Four Madagascar, Yemen, Haiti and Burundi were dealing with humanitarian situations.

Delivering vaccines in lower- and middle-income countries (LMICs) often requires getting vaccines to people in settings beset by conflict. By the end of 2022, of the 31 countries classified as having humanitarian emergency response plans, 26 were countries that Gavi supported with COVID-19 vaccine deliveries.

Across these countries, more than 250 million people are estimated to have needed humanitarian assistance. As of the end of 2022, half of all COVID-19 vaccine doses delivered in those 31 countries (411 million doses) were provided to their governments through COVAX, making it the largest source of vaccines in humanitarian contexts.

In 2020 and early 2021, Gavi collaborated with the United Nations' Inter-Agency Standing Committee (IASC) a forum for UN agencies including WHO and UNICEF that are involved in humanitarian work to develop the COVAX Humanitarian Buffer, a safety net of last resort to ensure access to COVID-19 vaccines for the most high-risk and vulnerable populations: those in humanitarian settings, including refugees, migrants, asylum seekers, stateless people and other vulnerable groups.

The pandemic disrupted many routine immunisation programmes, and even as those were being resumed in 2022, it was clear that COVID-19 vaccination would still be needed to be delivered by health systems. Gavi started working on supporting countries in integrating COVID-19 vaccination into regular health service delivery systems.

In July 2022, Gavi announced an additional US$667million in COVID-19 vaccine Delivery Support (CDS) that would, among other things, support the integration of COVID-19 vaccination and routine immunisation. The new funds were also used to tackle gaps in vaccine delivery and strengthen engagement.

For example, US$ 25 million was earmarked for direct support to civil society organisations to help unblock critical delivery, access and uptake bottlenecks, and reach under-served and unserved populations, including high-risk groups and those in humanitarian settings. Another US$ 30 million was reserved for emergency funding to be jointly managed with the CoVDP for immediate needs in the 34 low-coverage countries

This funding provided important health system strengthening benefits in many countries 71% of lower-income countries supported by COVAX reported strengthening of their cold chain infrastructure, while 76% were able to make progress in the digitisation of health data. A further 62% of countries reported integrating COVID-19 vaccination into their routine immunisation programmes.

One country that saw its health system strengthened through COVID-19 vaccine delivery was Somalia. In January 2022, the COVID-19 vaccine coverage rate in Somalia was just 5%. Campaigns enabled 90% of the high-risk and older adult population to be reached, and CDS funding was used to help scale up the country's cold-chain capacity. By May 2023, the country's COVID-19 vaccine coverage rate had reached 41%.

The investments made to boost COVID-19 vaccine delivery have had collateral benefits, including building an online digital system and dashboard to allow real-time vaccination monitoring; training staff in risk communication and community engagement; and procuring and installing four ultra-cold chain units and 25 solar direct drive vaccinerefrigerators that rely on solar energy rather than mains electricity.

Read the new Gavi Analysis Paper, Learning from COVID-19 to support vaccine delivery during future health emergencies, here:https://gavi.org/news-resources/knowledge-products/learning-covid-19-support-vaccine-delivery-during-future-health-emergencies

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Five key factors that allowed COVAX to deliver two billion COVID-19 vaccines - Gavi, the Vaccine Alliance

PORTLAND, Ore. The Oregon Health and Science Universityreleased a groundbreaking study which reveals switching arms for multi-dose COVID-19 vaccinations can boost immune response. The new study could change the way vaccines are handled in the future.

The idea started during the height of the pandemic when the newly formed vaccine was in high demand and in its early stages of research, according to OHSU associate professor of medicine Dr. Marcel Curlin.

Many people came through and there was a big rush to get vaccinated. We saw an opportunity to study something that we didn't know much about, Curlin said. So, we were looking at immune responses to COVID and vaccinations.

Once the vaccines became available in 2020, many people wondered whether alternating arms would make any difference.

The arm randomization was just sort of an afterthought, Curlin said. We knew that we were vaccinating in random arms, but we didn't know if it mattered. We always assumed that it didn't.

OHSU started measuring the antibody response of 947 people who received two-dose COVID vaccinations.

Curlin said they divided the group roughly in half, randomized them and asked one group to receive the contralateral or a shot in each arm while the other group received the shot in the same arm.

The results found when participants switched arms for each dose, they had 1 1/2 to two times more antibody levels in their blood.

Any small increase of antibody levels like a two-fold increase would translate into a mortality benefit for those that are most vulnerable to COVID or those most likely to experience a bad outcome. said Curlin.

OHSU professor of Pediatrics Dawn Nolt echoed that statement and added that the study could potentially help those who are more reluctant to receive the vaccination.

No promises to parents, but it could be that this increased immune response that we're seeing by alternating the site could mean one or two less doses for their child. said Nolt.

Participants also said the study could encourage more people to get vaccinated.

The more efficient you can make the vaccination process, the fewer times that people have to get vaccinated in order to be effective and the more likely they are to get the vaccine. said participant George Keepers.

Researchers said the improved immune response could be similar for other multidose vaccinations, though a further study would need to be conducted.

The full study from OHSU has been published in The Journal of Clinical Investigation.

See more here:

OHSU study finds greater antibody response when switching arms for multi-dose vaccination - KGW.com

By Michael Nguyen, PhD

Lipid nanoparticles (LNPs) have played a crucial role in the advancement of vaccine development, especially in the context of the COVID-19 pandemic. These LNPs have demonstrated their efficacy in delivering mRNA, which has significantly accelerated the vaccine development process. Additionally, LNPs are now being investigated as carriers for a range of therapeutics, offering a flexible and adaptable approach to vaccine creation.

The utilization of mRNA-LNPs has enabled governments to expedite the pharmaceutical development process and ultimately save lives during the ongoing COVID-19 crisis. By encapsulating the mRNA within LNPs, scientists have been able to protect the fragile genetic material from degradation and enhance its delivery to target cells. This has resulted in the successful development and deployment of mRNA-based COVID-19 vaccines, such as the Pfizer-BioNTech and Moderna vaccines.

The benefits of mRNA-LNPs extend beyond their application in COVID-19 vaccines. LNPs can be tailored to encapsulate various types of therapeutic molecules, including proteins, small molecules, and nucleic acids. This versatility makes LNPs a promising platform for the development of vaccines against other infectious diseases, as well as for the delivery of personalized medicine and gene therapies.

Explore how the success of mRNA-LNP vaccines is paving the way for future use in a wide range of therapeutic applications by accessing the full article below.

See the article here:

The Heroes Of Vaccine Development Lipid Nanoparticles - BioProcess Online

A limited outbreak of measles in Israel continues to grow with the Health Ministry announcing that four more cases were diagnosed in recent days. In total, 18 people have been found to have the contagious and potentially life-threatening respiratory disease since December 2023.

The first newly detected case involves a tourist from Russia who was at the emergency room at Barzilai Medical Center on February 5 from 8:30 p.m. until February 6 at 1 a.m.

The second is a boy from Holon who returned from Azerbaijan and was in the emergency department of Wolfson Medical Center from February 9 at 5 p.m. until February 10 at 4 a.m.; hed been vaccinated with one dose of the measles vaccine. The third contracted the disease from another person in the Haifa region who rode Egged bus 12 in Kiryat Yam on February 9, boarding at 12 p.m.

The fourth case is a toddler who was vaccinated with a single dose of the measles vaccine, which is appropriate for their age according to Health Ministry guidelines.

The ministry is carrying out an epidemiological investigation for each detected case. Anyone who suspects they were in proximity to a person with measles should call the ministry at 5400*. If someone develops symptoms, they should isolate themselves and be in touch with a doctor or hospital. The ministry urges Israelis to get the full set of measles vaccine shots.

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Measles cases in Israel climb to 18 after 4 more diagnosed, says Health Ministry - The Times of Israel

But shes not talking about the Covid vaccine. Shes praising a new shot against RSV.

RSV, or respiratory syncytial virus, usually hits in fall and winter. Its mild for most people but lethal for some especially babies and older people. In a typical year, according to the CDC, as many as 80,000 children under age 5 are hospitalized, and between 100 and 300 kids die. For those 65 and over, there are up to 160,000 hospitalizations a year, and 6,000 to 10,000 deaths.

But ahead of this RSV season, for the first time ever, immunization was finally approved for the most vulnerable groups of Americans, young and old. It was also recommended for those late in pregnancy, which would protect infants from birth.

Would people get the jab? As this RSV season winds down, the answer is that by and large, they did not.

The latest data from the CDC shows that only 16 percent of eligible pregnant people got vaccinated. Among the over 60 population, it was just over one in five. And among babies and eligible young children, the uptake was low, the CDC said.

Four years after Covid hit and fueled growing vaccine hesitancy, the rollout of the RSV vaccine this fall and winter offered a case study unfolding in real time. At issue was whether the public health and medical communities had acquired the skills, speed and agility needed to counter malicious misinformation before it took hold in the publics mind.

A series of organizations and strategies sprang up, both online and off, to debunk misinformation or prebunk it or tackle it in some other way. The action has not just been on TikTok but on WhatsApp, Google and in local communities across the country. But it hasnt been enough to rebuild trust among an increasingly skeptical nation, particularly on a new vaccine against an old disease.

If the question is, is the public health community better prepared than it was three years ago? I can answer yes, said Ashish Jha, back at his post as dean of Brown Universitys School of Public Health after serving for a year as the Biden administrations Covid response coordinator.

But, Jha added, doctors, nurses, public health officers and government agencies like the Centers for Disease Control, are operating in a challenging environment where too many downplay the winter respiratory season. These minimizers dont acknowledge just how lethal such diseases, including RSV, can be for the high-risk population, adding, Its been very hard to break through that wall of bad information.

The science of countering misinformation is still young.

All sorts of strategies that would seem to be potent turn out not to persuade people or they do, but the effect is ephemeral, with people reverting to their original false beliefs in as little as a week.

Still, health organizations have begun to mobilize since the tidal wave of Covid vaccine misinformation undermined demand for the shots and drove broader suspicion toward all vaccines, including routine childhood immunization for diseases like measles. But while clinicians and health groups are more alert to the threats, much of the population is so distrustful of public health and medicine inside or outside of government that any assertions of safety immediately get sucked into the conspiracy vortex.

The attack against RSV immunization during this first season wasnt at Covid vaccine proportions, but it is out there.

Despite 12 Deaths During Clinical Trials, CDC Signs Off on RSV Shots for Newborns, read an alert from the Childrens Health Defense, the anti-vaccine group founded by independent presidential candidate Robert F. Kennedy Jr. In fact, none of those deaths were caused by the shots, and there is ample data about their safety, including during pregnancy.

That didnt stop another vaccine critic physician named Peter McCullough from urging his 979,500 followers on X (the site formerly known as Twitter) not to get vaccinated. RSV in infancy easy to treat with nebulizers, he claimed. And there were others like him on various social media platforms.

If the question is, is the public health community better prepared than it was three years ago? I can answer yes, said Ashish Jha. | Drew Angerer/Getty Images

Many people have been seeking out information on RSV, according to the Public Health Communications Collaborative, which was formed by the CDC Foundation, the de Beaumont Foundation and Trust for Americas Health in 2020. The organization, which brought in additional partners, works to provide accurate and effective messaging to the public health community and tracks online trends. It has found that when people search online for information on RSV, they see both facts and false claims. And for many people, after the last few years of competing online claims, it can be hard to figure out which is which.

In one major victory for accuracy and the public health world, Google followed guidance from experts convened under the National Academy of Medicine and the World Health Organization. Those experts outlined how tech platforms can identify credible sources of health information that can be elevated online. Its not that nothing wrong or nefarious about RSV or any other health topic will ever get through Google search or YouTube, but these practices may make it less pervasive. For instance, if you google RSV, the first items that appear on the screen come from sources like the CDC, the Mayo Clinic, the American Lung Association not from some self-appointed vaccine expert posting jeremiads about fictitious vaccine hazards from his basement.

What we did was give [Google] a rubric and a blueprint to help them justify elevating credible sources, said Antonia Villarruel, the dean of the University of Pennsylvania School of Nursing and a co-author of the credible sources report. You get fact-based information as the first component of a search.

Still, there are plenty of other online venues where misinformation metastasizes.

Once these beliefs have taken root, its harder to disabuse people of them, said Richard Baron, the president and CEO of the American Board of Internal Medicine, which has a foundation that has spent the last few years looking at misinformation and distrust in medicine. And citing the FDA and CDC doesnt work for people who believe the narrative that the FDA and the government thats supposed to protect us is either captured by industry or in on the game.

Its hard to combat falsehoods that play on fear and distrust and division. Researchers have found that fact-checking also known as debunking is helpful for reaching those people who are uncertain or worried, who need more information but arent adamantly opposed to vaccines. Many of the people who started out hesitant about the Covid vaccine did end up getting it, an outcome that reflected both mandates and growing confidence in the safety as more people took the shots.

But debunking doesnt work so well on people who are dug in. Plus, by the time something gets fact-checked or debunked, its already circulating and has taken hold among some parts of the population.

Thats given rise to an effort to prebunk, or try to get ahead of the misinformation. Sometimes efforts are broad and largely intended to educate people (sometimes through quick online games such as the Bad News game or Go Viral) so their emotions and fears arent so easily manipulated on social media. It turns out we are hard-wired in ways that make it easier to petrify than to reassure.

The second kind of prebunking aims at either anticipating misinformation or at least detecting it so quickly that the public health community can counter it before it explodes.

With vaccines, its possible to prebunk and blunt some of the predictable tropes since theres a well-known anti-vax playbook of falsehoods. The various fictions include: Vaccines havent been thoroughly tested or they cause autism or they change human DNA or the side effects are worse than the disease or the vaccine gives you the disease or natural products boost immunity better than vaccines or vaccines are just a way for Big Pharma to make more money or vaccines damage fertility. (That last one is a particularly pernicious message given that the RSV vaccine is given during pregnancy.)

Those messages persist and proliferate, despite years of accelerating efforts to swat them down. And not all negative messaging can be anticipated. Did anyone really foresee that meme about Bill Gates inserting microchips in us via Covid vaccines? How about that wild claim that Covid vaccines contain eggs that hatch synthetic parasites that thrive inside the human body?

In other words, prebunking may work up to a point against predictable messages, but public health and medicine need a way of monitoring social media to rapidly identify newly emerging misinformation. The right messages say from trusted public figures who talk about why they are getting a certain vaccine or are giving it to their child need to get out fast.

Then you begin to build the confidence so that when that one crazy story comes in, it doesnt have the same impact, said Jha.

Several efforts to develop that kind of agility are emerging.

Among the most comprehensive is the initiative from the Public Health Communications Collaborative, which partners with the Public Good Projects, a health care nonprofit that does broad, rapid monitoring of social media and works with both influencers and public health organizations.

The Public Good Projects shares with clinicians, public health officials and others a monthly survey of the health disinformation landscape. But monthly isnt good enough when lies zip around the world in seconds. So Public Good now does more real-time monitoring, and when something bubbles up, the Collaborative shares it with health departments and agencies across the country about 30,000 people as of late autumn, each of whom has their own networks. The Collaborative also sends out best practices for fighting high-risk misinformation, without inadvertently amplifying falsehoods.

If the Collaborative is working on the public health side, another new initiative called Coalition for Trust in Health and Science is bringing together a large and growing group of public, private and nonprofit health organizations medical, clinician, science and health care industry groups along with more traditional public health organizations.

Given the magnitude of the challenge of misinformation/disinformation and distrust we felt like this would be the moment where you had to bring together the entire health ecosystem, said one of the founders, Reed Tuckson a well-known health consultant and physician who is also a co-founder of Black Coalition Against Covid. The organization, though drawing in a broad membership, is still in the early stages.

Other advocates have developed more ad hoc approaches.

A group called ThisIsOurShot and its sister site VacunateYa, organized by young doctors and nurses during Covid, promoted the RSV vaccine on social media. Factchequeado, a Spanish language fact-checking initiative, has created a WhatsApp chatbot so people can discern health fact from fiction in their own messages.

And another group is taking a different starting point altogether: listening to local communities themselves. What are they hearing about public health, and what do they need to know? Its called iHeard.

Starting in St. Louis, in conjunction with the public health school at Washington University, iHeard distributes a weekly survey to about 200 people, which can be filled out in about three minutes. It asks about everything from vaccines to contaminated pouches of apple sauce popular with young children. iHeard is now spreading to several other cities across the country.

We put in place a system, a kind of proactive community listening, to try to get a handle on what people were hearing and when new misinformation might enter the community, said Washington University public health professor Matthew Kreuter. It began focused on Covid but has pivoted to health more broadly.

The survey information is posted on a public-facing dashboard, and its shared with partners in health, education, government and social services. The team also produces messaging that can be used on social media where people in the community are more likely to see it than on a university dashboard. The whole program has the advantage of involving community voices, which build trust.

The RSV vaccines dont generate quite as much fury as Covid, for several reasons, including the fact that there are no mandates for this shot, not at jobs, not at schools.

The audience is also narrower: Shots are recommended for people over age 60 and those who are between 32 and 36 weeks pregnant so they can pass on antibodies to the fetus. Infants not protected in utero, and other young children at high risk can get monoclonal antibodies, which isnt technically a vaccine although it is an injection. Those monoclonal antibodies were in short supply this season, as this was one place where manufacturers apparently underestimated the demand or overestimated the already considerable hesitancy.

In addition, the target population for RSV shots people over 60, people having babies are likely to be connected to the health care system; theyre already patients. That means they are more likely to have a doctor, a nurse or other provider that they know and trust. Thats not the case for some of the more militant anti-vaxxers, who are distrustful of the whole medical establishment. Yet vaccination rates were low.

Finally, public health experts noted, anti-vaccination sentiment is so high right now that the disinformation makers dont have to go after RSV specifically to instill fear and mistrust in a new shot. It just got wrapped into the whole deepening anti-vaccine gestalt. Routine childhood immunization rates are now down to 93 percent for kindergarteners, below the 95 percent threshold the CDC says is needed to thwart disease outbreaks.

Theres a level of exhaustion, right? said Katy Evans, senior program officer at de Beaumont Foundation, one of the groups forming the Public Health Communication Collaborative. You want me to get three in some cases, three vaccines this fall: a Covid booster, a flu shot and an RSV vaccine. And if I am someone who doesnt really understand why those things are valuable, that feels like a big ask.

The relatively disappointing uptake on RSV vaccination underscores just how big an ask it was.

Ultimately fighting disinformation comes down to trust. Trust is what a lot of the malevolent messengers are trying to destroy, and trust is what the public health, scientific and clinical worlds have to rebuild. Thats a resource even more valuable than the smarter, faster, better tools being developed to combat misinformation and disinformation.

It cant just be about getting ahead of a wacky narrative that resonates with people who no longer trust doctors or scientists, said ABIMs Baron. People are believing this stuff because it is consistent with a narrative they already believe. And we have to get better in constructing a different narrative.

See more here:

The Next Front in the Vaccine Wars - POLITICO

If youve presented the same arm for every dose of a particular vaccine, you may want to reconsider. Alternating arms may produce a more powerful immune response, a new study suggests.

The researchers studied responses to the first two doses of Covid-19 vaccines. Those who alternated arms showed a small increase in immunity over those who got both doses in the same arm.

[HSE chief repeats call for people to avail of flu vaccine]

For individuals who respond poorly to vaccines because of age or health conditions, even a small boost may turn out to be significant, the researchers said. At this point in the pandemic, with most people having had multiple vaccine doses or infections, alternating arms for Covid vaccines may not offer much benefit. Yet, if confirmed by further study, the results could have implications for all multi-dose vaccines, including childhood immunisations.

Im not making recommendations at this point, because we need to understand this a lot better, said Dr Marcel Curlin, an infectious disease physician at Oregon Health and Science University who led the work. But, all things being equal, we ought to consider switching up the arms.

[After death of man from measles, CMO concerned over high risk of outbreak in Ireland]

The few studies comparing the two approaches have been small and have produced mixed results. And none of the studies have shown a big difference in immunity.

In the new study, Dr Curlin and his colleagues repeatedly measured antibody levels in 54 pairs of university employees matched for age, gender and the time after vaccination.

[The worrying increase of vaccine hesitancy]

The participants, part of a larger research project, were randomised to get the second dose in the same arm as the first dose or in the opposite arm. The researchers excluded anyone who became infected with Covid during the study.

Switching the arms increased blood antibody levels by as much as fourfold, the scientists found. The results were published in The Journal of Clinical Investigation.

The immune response was stronger against both the original coronavirus and against the omicron variant, which emerged roughly a year after the authorisation of the first Covid vaccines. - This article originally appeared in the New York Times

Go here to see the original:

Could switching arms for vaccinations increase immunity? The Irish Times - The Irish Times