In a recent study published in Vaccines, researchers assessed the efficiency of a hybrid vaccine against influenza and coronavirus disease 2019 (COVID-19) viruses.
People worldwide are exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the influenza virus. Therefore the development of a two-in-one vaccine that could elicit protection against both these infections is a subject of great interest.
In the present study, researchers developed a hybrid vaccine using influenza virus-like particle (VLP) vaccine incorporated with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 receptor-binding domain (RBD) fused to granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein.
The team developed a fusion protein gene by fusing deoxyribonucleic acid (DNA) sequences that are specific to the SARS-CoV-2 spike (S) protein RBD domain, GPI-anchor signal derived from human CD59, and mouse GM-CSF. Flow cytometry was subsequently performed to demonstrate the expression of the fusion protein on the transfected CHO-S cells. The team also assessed whether the anti-RBD antibodies present in the convalescent sera collected from SARS-CoV-2-infected patients identified the RBD of the fusion protein by performing an enzyme-linked immunosorbent assay (ELISA).
The team subsequently evaluated whether the fusion protein had two functions as GM-CSF and while also binding to human ACE2. Furthermore, the researchers developed the VLP hybrid vaccine by incorporating the influenza VLP with GPI-RBD-GM-CSF and GPI-interleukin (IL)-12 via protein transfer. Flow cytometry was also conducted using anti-GM-CSF antibodies and fluorochrome-conjugated anti-IL-12 to verify the dual incorporation of the GPI-RBD-GM-CSF and GPI-IL-12 onto VLPs. The retention of function by VLP-incorporated GM-CSF was verified by culturing mouse bone marrow-derived dendritic cells (BDMC), followed by the measurement of BMDC proliferation using XTT assay.
The team tested the induction of antibody response by the GPI-RBD-GM-CSF fusion protein by immunizing BALB/c mice with either the fusion protein or VLPs incorporated into the fusion protein along with GPI-IL-12. VLP without cytokines or commercially available RBD was used as control. The team administered a booster dose to the mice population two to four weeks after the first dose. Blood samples were obtained from the mice every two to four weeks in order to estimate antibody titer, virus neutralization assays, and ACE2 binding inhibition.
The study results showed that almost 76% of the fusion protein was secreted from the cell surface of the RBD-GM-CSF fusion protein, which suggested that the fusion protein was anchored into the cell membrane through a GPI tail. The RBD in the fusion protein exhibited ACE2 binding activity while RBD-specific neutralizing antibodies could bind to GPI-RBD-GM-CSF present on the CHO-S cell transfectants.
Antibodies found in the sera of COVID-19 patients could efficiently bind to the GPI-RBD-GM-CSF. Moreover, ELISA confirmed that RBD from the purified fusion protein retained its receptor binding activity. Additionally, the XTT assay showed that GPI-RBD-GM-CSF that was incorporated in the VLP vaccine could effectively stimulate BMDC proliferation.
The team observed that the VLP hybrid vaccine elicited a significant antibody response after the administration of the GPI-RBD-GM-CSF booster dose. The antibody response elicited by the fusion protein was similar in both the intramuscular and subcutaneous routes of vaccine administration. The antibodies selectively bound to the CHO-S cells which expressed the fusion protein but not to the untransfected CHO-S cells. This indicated the high specificity of the antibody response to the fusion protein.
The team also noted that the purified GPI-RBD-GM-CSF fusion protein-induced antibody levels that were comparable to those elicited by the VLP hybrid vaccine. However, the neutralizing antibody titers were considerably low in the mice that were immunized by only the GPI-RBD-GM-CSF protein without any VLP. This suggested that fusion protein that was incorporated with VLP elicited a more robust neutralizing antibody response as compared to that of the soluble fusion protein.
Furthermore, the purified GPI-RBD-GM-CSF fusion protein alone or when incorporated with VLPs induced a substantial antibody response. On its own, the fusion protein induced a primarily Th2 type immunoglobulin 1 (IgG1) response while the hybrid VLP vaccine elicited both IgG1 and IgG2a responses. Notably, the incorporation of GPI-IL-12 into the hybrid VLP vaccine did not affect the IgG2a response.
The team also observed that the hybrid vaccine by itself and the hybrid vaccine without IL-12 elicited robust antibody responses against the RBD as well as the influenza VLP antigens. These antibodies could sufficiently neutralize live virus infection when assessed via a plaque reduction neutralization titer (PRNT) assay. Moreover, substantially reduced viral replication was observed in the hybrid vaccine-treated mice as compared to the VLP-treated ones.
Overall, the study findings showed that the delivery of SARS-CoV-2 RBD protein via influenza VLPs along with cytokine adjuvants served as an effective platform for the development of multivalent vaccines. The researchers believe that the usage of immobilized cytokines as an adjuvant will help elicit anti-viral immunity with minimal adverse effects.
Journal reference:
Read the original:
Effectiveness of a hybrid vaccine against COVID-19 and influenza - News-Medical.Net
- The Health Department website was attacked in the middle of the coronavirus pandemic - Vox.com [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Defining Coronavirus Symptoms: From Mild To Moderate To Severe : Goats and Soda - NPR [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- What Are the Symptoms of a Coronavirus Infection? - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Hotels Were Rolling Out Tools to Help Calm Travelers. Then Coronavirus Hit. - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- The Coronavirus, by the Numbers - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Opinion: Early Coronavirus Testing Failures Will Cost Lives - NPR [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus Cases Surge in U.S. and Europe - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Two Emergency Room Doctors Are in Critical Condition With Coronavirus - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus: Over 1000 Cases Now In U.S., And 'It's Going To Get Worse,' Fauci Says - NPR [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- China Spins Tale That the U.S. Army Started the Coronavirus Epidemic - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Everything to Know About the Coronavirus in the United States - The Cut [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus closed this school. The kids have special needs: 'You can't Netflix them all day.' - USA TODAY [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- How Long Can The Coronavirus Live On Surfaces? : Shots - Health News - NPR [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus Cost to Businesses and Workers: It Has All Gone to Hell - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- In the U.S., More Than 300 Coronavirus Cases Are Confirmed - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- How Jair Bolsonaro's Son, Eduardo, Confirmed His Father's Positive Coronavirus Test to Fox News, Then Lied About It - The Intercept [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- De Blasio Resisted on Coronavirus. Then Aides Said Theyd Quit. - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Trump Is Tested for Coronavirus, and Experts Ask: What Took So Long? - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Live Coronavirus Updates and Coverage - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus Threatens Americans With Underlying Conditions - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus Capitalism and How to Beat It - The Intercept [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- An essential reading guide to understand the coronavirus - Vox.com [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- N.Y.C.s Economy Could be Ravaged by Coronavirus Outbreak - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- 'A ticking time bomb': Scientists worry about coronavirus spread in Africa - Science Magazine [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- How coronavirus is affecting the restaurant business, in one chart - Vox.com [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus Map: How To Track Coronavirus Spread Across The Globe - Forbes [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Coronavirus Testing Website Goes Live and Quickly Hits Capacity - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Map: How Many Cases Of Coronavirus Are There In Each US State? : Shots - Health News - NPR [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- Live Coronavirus Updates and Coverage Globally - The New York Times [Last Updated On: March 16th, 2020] [Originally Added On: March 16th, 2020]
- This Is How the Coronavirus Will Destroy the Economy - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Every Star and Public Figure Diagnosed with COVID-19: A Running List - The Daily Beast [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Coronavirus: What you need to know - Fox News [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Travel updates: which countries have coronavirus restrictions and FCO warnings in place? - The Guardian [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Staff angered as Charter prohibits working from home despite spread of coronavirus - TechCrunch [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- If coronavirus scares you, read this to take control over your health anxiety - The Guardian [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- San Francisco and Bay Area will shelter in place to slow coronavirus spread - The Verge [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Coronavirus spreading fastest in UK in London - The Guardian [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Businesses Face a New Coronavirus Threat: Shrinking Access to Credit - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Welcome to Marriage During the Coronavirus - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Sweeping restrictions take effect in coronavirus response as health officials warn US is at a tipping point - CNN [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- How Long Will the Coronavirus Outbreak and Shutdown Last? - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- 201920 coronavirus pandemic - Wikipedia [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Coronavirus - World Health Organization [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- What Is Coronavirus? | HowStuffWorks [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Coronavirus | CISA [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Is there a cure for the new coronavirus? - Livescience.com [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Shelter in Place: Some Residents in Bay Area Ordered to Stay Home - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Tracking the Impact of the Coronavirus on the U.S. - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- 8 Things Parents Should Know About The Coronavirus: Life Kit - NPR [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Spain, on Lockdown, Weighs Liberties Against Containing Coronavirus - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- New Yorks Nightlife Shuttered to Curb Coronavirus - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- How best to fight the economic impact of the coronavirus pandemic - The Guardian [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Heres whos most at risk from the novel coronavirus - The Verge [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Closing Down the Schools Over Coronavirus - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- The U.S. Economy Cant Withstand the Coronavirus by Itself - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- U.S. Lags in Coronavirus Testing After Slow Response to Outbreak - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- U.K. Steps Up Coronavirus Prevention, But Its Hospitals Have Already Been Strained - NPR [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Coronavirus panic is clearing out grocery stores; heres how workers are handling it - Vox.com [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Tracking the Coronavirus: How Crowded Asian Cities Tackled an Epidemic - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Coronavirus Treatment: Hundreds of Scientists Scramble to Find One - The New York Times [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Coronavirus cases have dropped sharply in South Korea. What's the secret to its success? - Science Magazine [Last Updated On: March 17th, 2020] [Originally Added On: March 17th, 2020]
- Facebook was marking legitimate news articles about the coronavirus as spam due to a software bug - The Verge [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- The Single Most Important Lesson From the 1918 Influenza - The New York Times [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- How to Protect Older People From the Coronavirus - The New York Times [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Coronavirus Is Killing Iranians. So Are Trump's Brutal Sanctions. - The Intercept [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Is there a cure for coronavirus? Why Covid-19 is so hard to treat - Vox.com [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Coronavirus: The math behind why we need social distancing, starting right now - Vox.com [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Europeans Erect Borders Against Coronavirus, but the Enemy Is Already Within - The New York Times [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Some of the last people on earth to hear about the coronavirus pandemic are going to be told on live TV - CNN [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Why the US is still struggling to test for the coronavirus - The Verge [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- The Coronavirus Is Here to Stay, So What Happens Next? - The New York Times [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Coronavirus in the U.S. - The New York Times [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Watch the Footprint of Coronavirus Spread Across Countries - The New York Times [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Coronavirus Briefing: What Happened Today - The New York Times [Last Updated On: March 18th, 2020] [Originally Added On: March 18th, 2020]
- Why the Covid-19 coronavirus is worse than the flu, in one chart - Vox.com [Last Updated On: March 21st, 2020] [Originally Added On: March 21st, 2020]
- Fact-Checking 5 Trump Administration Claims On The Coronavirus Pandemic - NPR [Last Updated On: March 21st, 2020] [Originally Added On: March 21st, 2020]
- Trump has scoreboard obsession. It hasnt worked with coronavirus - POLITICO [Last Updated On: March 21st, 2020] [Originally Added On: March 21st, 2020]
- Here's What Is In The 'Families First' Coronavirus Aid Package Trump Approved - NPR [Last Updated On: March 21st, 2020] [Originally Added On: March 21st, 2020]
- Young Adults Come to Grips With Coronavirus Health Risks - The New York Times [Last Updated On: March 21st, 2020] [Originally Added On: March 21st, 2020]
- Which Country Has Flattened the Curve for the Coronavirus? - The New York Times [Last Updated On: March 21st, 2020] [Originally Added On: March 21st, 2020]