Vaccine Research and Development to Advance Pandemic and Seasonal Influenza Preparedness and Response Lessons from COVID-19 (2022) / Chapter Skim
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2 Basic and Translational Science
2 Basic and Translational Science
Pages 37-62
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The third section considers how lessons learned from the devel BOX 2-1 Basic and Translational Science: Lessons Learned from the COVID-19 Pandemic • Previous investments in basic research were essential for rapid COVID-19 vaccine development. • Existing centers of excellence with established off-the-shelf protocols and know-how were able to move quickly to conduct needed research on novel vaccines for COVID-19.
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As discussed in Chapter 1, current seasonal and pandemic influenza vaccines are based on traditional vaccine platforms and concepts that induce strain-specific immunity. The seasonal vaccines require annual reformulation and readministration, or inclusion of a novel matched virus in case of a pandemic (Krammer and Palese, 2015)
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. The Gamaleya National Research Centre for Epidemiology and Microbiology in Russia developed a heterologous recombinant adenovirus vaccine based on recombinant adenovirus type 26 and type 5 encoding the full-length spike protein of SARS-CoV-2 (Logunov et al., 2021)
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The first vaccine, produced by Pfizer-BioNTech, was authorized 8 months after clinical trials began (Ball, 2021) . COVID-19 vaccine development was rapid but not enough to prevent hundreds of millions of infections (WHO, 2021a)
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including off-the-shelf vaccines that can be strategically deployed to slow down the global spread of infection, and response, activating the rapid development and manufacture of highly effective vaccines. CURRENT INFLUENZA VACCINES Influenza vaccines have been used for more than 50 years and provide moderate protection with a vaccine effectiveness rate varying between 10 and 60 percent (Paules and Fauci, 2019)
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Production of Seasonal Influenza Vaccines in 2021 As discussed in Chapter 1, the vast majority of the available vaccines against seasonal influenza viruses in 2021 are inactivated egg-grown vaccines, with 15.5 percent produced using cell culture platforms (Sparrow et al., 2021)
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In a pandemic context, these barriers may be overcome by access to reserve funding. The committee recognizes that the current manufacturing capacity, availability, and use of egg-based vaccines has held back innovation of novel platforms for influenza vaccines, particularly when contrasted with COVID-19 vaccine development.
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. A number of factors will influence whether mRNA vaccine platforms are adopted for influenza vaccine development, including relative efficacy, manufacturing capacity, and costs of manufacture and distribution.
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Conclusion 2-1: A priority focus for future research on influenza vac cines is how to overcome issues associated with viral antigenic drift and annual vaccination, and the potential of novel vaccine platforms to circumvent such effects. Improved characterization of B cell responses may help to validate current theories that vaccines recall existing mem ory B cells but do not efficiently induce de novo B cell responses against variant epitopes in new vaccine strains.
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Early clinical trials (phase I and II) are critical for the generation of safety and immunogenicity data required to identify promising antigens and platform constructs and to select candidates for phase III efficacy trials.
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However, the usefulness of broadly protective influenza virus vaccines/UIV is not limited to pandemic preparedness. Highly effective UIV candidates would also abolish the need for matched seasonal vac cines and thereby increase vaccine uptake globally, leading to a reduced burden of seasonal influenza on global health and decreased susceptibil ity of the global population against zoonotic influenza virus outbreaks or emerging pandemic influenza viruses.
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. For novel influenza pandemic strains, fluctuations in funding combined with the need to wait until there is active transmission to test vaccine efficacy significantly slows vaccine development, as seen with the Ebola vaccine.
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Expanding the number of manufacturers globally can also aid in situations where there are shortages caused by other factors unrelated to a pandemic, such as infrastructure damage caused by natural disasters. Recombinant protein vaccines may be a cost-effective and efficient way of producing influenza vaccines compared to the mRNA platform as they have already been shown to be safe and effective and the infrastructure for production is already in place (Dunkle and Izikson, 2016; Pollet et al., 2021)
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Allowing sufficient flexibility in the details of assay design, especially for later-stage development, is essential to allow for the refinement of assays that is needed to achieve the automation, throughput, and performance standards needed to support the large-scale clinical trials that lead to vaccine authorization or licensure. After basic research characterization of potential targets for vaccines, the first phase of vaccine development involves preclinical research, including both in vitro work and animal studies to test safety and immunogenicity.
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This discourages pharmaceutical companies from engaging in next-generation influenza virus vaccine development. Having immune correlates of protection to assess in clinical trials would streamline the vaccine development pipeline.
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. When updating a vaccine containing new antigens for the seasonal influenza vaccine, manufacturers submit a supplement for their existing vaccine license.
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There are several candidates for universal influenza vaccines and several new vaccine platforms, but clinical testing is a bottleneck that should be prioritized. Clinical development should be carried out on a global scale, requiring global coordination.
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Recommendation 2-4: National regulators should engage with the vac cine industry and academic researchers in the development, standard ization, and implementation of innovative assays to evaluate vaccines that induce immunity through mechanisms other than strain-specific neutralizing hemagglutination-inhibiting antibodies in order to reach consensus on the validation of these assays that will allow approval or licensure of influenza vaccines based on a broader range of assays that reflect induction of immunity. REFERENCES Al Kaabi, N., Y
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2018. Cell culture-derived influenza vaccines in the severe 2017-2018 epidemic season: A step towards improved influenza vaccine effectiveness.
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2020. A decade in review: A systematic review of universal influenza vaccines in clinical trials during the 2010 decade.
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2019. Development of universal influenza vaccines targeting conserved viral proteins.
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standard-dose egg-based quadrivalent influenza vaccines during the 2018–19 influenza season in the United States. Vaccines 9(2)
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2017. Chasing seasonal influenza -- the need for a universal influenza vaccine.
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2021. Global production capacity of seasonal and pandemic influenza vaccines in 2019.
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neutralizing antibody responses elicited by 2018–2019 season quadrivalent influenza vaccines derived from eggs, cells, and recombinant hemagglutinin. Clinical Infectious Diseases.
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2017. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains.
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