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Flu News Friday 4/9/21

Read the latest on influenza vaccines in this week’s roundup.

Image credit: Real-time tracking of influenza A/H3N2 evolution using data from GISAID. Built with nextstrain/seasonal-flu, maintained by Jover Lee, Richard Neher and Trevor Bedford. Enabled by data from GISAID.
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The Latest in Influenza Vaccines

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1. A ‘variant-proof’ vaccine [Podcast]
Elana Gordon, The World / April 6, 2021

The emergence of SARS-CoV-2 variants has spurred increased motivation to develop universal, broadly protective vaccines. This podcast discusses the work to develop these “variant-proof” vaccines, building from existing efforts to achieve universal influenza vaccines. Technologies such as AI and Next-Generation Sequencing could accelerate the development of these variant-proof vaccines, but global coordination and collaboration will be essential for ‘cracking the universal code’ in preparing for Disease X.

2. The Collaboratory: How sharing tools and technologies can shorten the timeline for global health R&D
Lynda Stuart, The Gates Foundation / April 2, 2021

Lynda Stuart, Deputy Director of Vaccines & Human Immunology for the Bill & Melinda Gates Foundation, discusses the importance of collaboration and translational research in bridging the Valley of Death for new vaccine technologies and other health innovations. She calls for this convergence of ideas and disciplines to be less “ad hoc” and more “baked into the system.”

3. Preventing the next pandemic: the search for a universal flu vaccine
Rachel Brazil, The Pharmaceutical Journal / April 1, 2021

From the COVID-19 pandemic to the recent avian flu cases in humans, it is clear we need to develop a universal influenza vaccine to protect us against future influenza pandemics. This article outlines the current challenges of seasonal flu vaccines and what is being done to overcome them and develop broadly protective UIVs, not only targeting the surface protein hemagglutinin for B cell responses, but also neuraminidase for T cell responses.

4. Single-Dose COVID-19 Nasal Vaccine Limits Infection in Monkeys
National Institute of Allergy & Infectious Diseases / April 1, 2021

Scientists from Washington University School of Medicine and the National Institute of Allergy & Infectious Diseases developed a single dose, adenovirus vectored, SARS-CoV-2 vaccine, designed to be administered intranasally. The study found only a single dose of the vaccine demonstrated immunogenicity and protected rhesus macaques from infection in the respiratory tract. While this is a vaccine development for SARS-CoV-2, this breakthrough could potentially be used for vaccines for other diseases, such as influenza, in the future.

5. Balanced Cellular and Humoral Immune Responses Targeting Multiple Antigens in Adults Receiving a Quadrivalent Inactivated Influenza Vaccine [Preprint]
Yu et al., / April 2, 2021

Scientists studied T cell and B cell immune responses in the Flucelvax quadrivalent inactivated flu vaccine. Containing two influenza B and two influenza A strains, the vaccine was developed using mammalian cell lines instead of egg-based approaches, allowing for a decreased production timeframe that could be scaled out to larger populations. The vaccine led to increased CD8+ T cell responses to conserved core domains of the virus in all four strains. CD4+ and CD8+ responses were still present after 15 and 91 days post-vaccination, including responses to both Hemagglutinin and non-Hemagglutinin viral proteins. No intra-vaccine interference was detected.

6. Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
Marriott et al., npj Vaccines / March 29, 2021

Live attenuated influenza vaccines (LAIVs) and inactivated influenza vaccines are the current vaccine approaches used for seasonal flu. LAIVs are constructed through reverse genetics and are administered intranasally. Unlike inactivated flu vaccines, LAIVs replicate in the upper respiratory tract and generate both humoral and cell-mediated immune responses; making them a consideration for the development of universal flu vaccines. Using a ferret animal model, scientists demonstrated that a monovalent H1N1pdm09-specific LAIV was fully protective against a H1N1pdm09 challenge and reduced the severity of a subsequent challenge with the H3N2 subtype, providing insights regarding cross-reactive T cell responses for UIVs.

7. Design of bacterially expressed influenza stem immunogens displayed on Msdps2 protein nanoparticles [Preprint]
Kar et al., bioRxiv / March 15, 2021

Scientists displayed a pH1HA10-Foldon HA stem immunogen on Msdps2 protein nanoparticles. The structure of the fused Msdps2-pH1HA10 nanoparticle was determined through cryo-electron microscopy (cryo-EM). Mice were immunized with the nanoparticle antigen and findings suggest that it was immunogenic; future studies in mice and ferrets will be carried out to validate the results.

8. Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
Cohen et al., PLOS One / March 4, 2021

Scientists covalently attached a diverse array of HA ectodomain trimers from group 1 and group 2 influenza A strains to form both mosaic virus-like particles (VLPs) and mosaic nanoparticles (NP) using the SpyCatcher technology. Compared to homotypic VLPs and NPs, the heterotypic mosaic SpyCatcher-VLPs and SpyCatcher-NPs did not elicit a larger humoral response. The authors conclude the covalent display of HAs from currently-circulating influenza strains could be a viable alternative to current seasonal flu vaccine strategies, but in order to be used for universal influenza vaccines, the approach would need to be modified. The study also provides insights for the use of the “plug and play” SpyCatcher technology for the development of future influenza vaccines.

9. First-in-human clinical trial confirms novel HIV vaccine approach developed by IAVI and Scripps Research
The International AIDS Vaccine Initiative / February 3, 2021

Scripps Research and the International AIDS Vaccine Initiative (IAVI) announced a successful phase I clinical trial for an HIV nanoparticle vaccine candidate. Using reverse vaccinology, the eOD-GT8 60mer immunogen was designed to activate naïve B cells that produce precursors to a type of broadly neutralizing antibody (bnAb). Future studies are planned to study additional HIV vaccines that elicit more types of bnAbs, while scientists believe this particular approach could be extended to vaccine development for other diseases such as influenza. Moderna will also apply their mRNA vaccine platform for delivering the HIV immunogen; a phase I clinical trial will start during the third quarter of 2021.

10. Funding Opportunities and Information

How research funders are tackling coronavirus disruption
Emma Stoye, Nature / April 17, 2020

Surveillance and Response to Avian and Pandemic Influenza by National Health Authorities outside the United States
National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention / Closes May 4, 2021

Collaborative Program Grant for Multidisciplinary Teams
National Institute of General Medical Sciences / Due May 27, 2021

Building collaboration at the physics of life interface: 2021 outline stage
Engineering and Physical Sciences Research Council (EPSRC), Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council (MRC) / Closes June 2, 2021