Tracking progress in universal influenza vaccine development

Ostrowsky, Julie; Arpey, Meredith; Moore, Kristine A.; Osterholm, Michael T.; Friede, Martin; Gordon, Jennifer L.; Higgins, Deborah; Molto-Lopez, Julia; Seals, Jonathan R.; Bresee, Joseph S.

doi:10.1016/j.coviro.2020.02.003

Cited by 19 publications

(24 citation statements)

References 25 publications

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“…Although vaccines against the influenza virus were developed as early as the 1940′s, the use of inactivated wild-type viruses as vaccines are still the best method of inducing protection in the human population 33 . Current seasonal wild-type A(H3N2) influenza vaccines are typically strain specific and sometimes induce a narrow range of antigenic breadth against co-circulating viral variants 1,30 . However, there are some eras of H3N2 influenza virus circulation where the wild-type vaccines elicit highly cross-reactive antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Speed of production is critical and there would be less pressure if vaccine manufacturers could produce a vaccine that elicits long-lived protective immune responses 33,35 . In 2018, the U.S. government was tasked with expanding the capacity for more agile and rapid vaccine production methods to advance the development of broadly reactive vaccine candidates 30 . The accelerated pace of generating and selecting up to date next-generation COBRA-based antigens would be highly advantageous over traditional methods of selecting wild-type vaccine candidate viruses.…”

Section: Discussionmentioning

confidence: 99%

“…Aside from potentially reducing the need to update vaccines on an annual basis, technologies like the COBRA methodology provide a promising solution to increase the protection offered by seasonal vaccines against currently co-circulating strains as well as future emerging isolates. The current vaccine manufacturing process takes about 6-8 months from strain selection to vaccine availability and any delays in strain recommendation or antigenic characterization can lead to devastating reductions in the vaccine supply 1,30 . Thus, having a broadly reactive vaccine candidate, that has already been antigenically characterized, optimized for production, and is "shelf-ready" would save manufacturers a considerable amount of stress and time, while allowing for year-round production of more doses of vaccine.…”

mentioning

confidence: 99%

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Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

Allen

Ross

2021

Sci Rep

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While vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

Allen

Ross

2021

Sci Rep

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“…The main premise for universal influenza virus vaccines is to boost antibody responses that target conserved, yet less accessible, regions of the virus [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. The HA head domain is the primary target of immune responses after infection and vaccination.…”

Section: Universal Influenza Virus Vaccinesmentioning

confidence: 99%

Animal Models Utilized for the Development of Influenza Virus Vaccines

Roubidoux

Schultz‐Cherry

2021

Vaccines

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Animal models have been an important tool for the development of influenza virus vaccines since the 1940s. Over the past 80 years, influenza virus vaccines have evolved into more complex formulations, including trivalent and quadrivalent inactivated vaccines, live-attenuated vaccines, and subunit vaccines. However, annual effectiveness data shows that current vaccines have varying levels of protection that range between 40–60% and must be reformulated every few years to combat antigenic drift. To address these issues, novel influenza virus vaccines are currently in development. These vaccines rely heavily on animal models to determine efficacy and immunogenicity. In this review, we describe seasonal and novel influenza virus vaccines and highlight important animal models used to develop them.

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“…Current seasonal influenza vaccines are effective when vaccine strains are matched with circulating strains [ 2 , 3 ]. However, there is little to no cross-protection against antigenic variants, emerging pandemic or zoonotic outbreak strains [ 4 ]. There is therefore tremendous interest in the development of novel “universal” vaccines, that would significantly expand protection to most or all influenza viruses.…”

Section: Introductionmentioning

confidence: 99%

Aggregation by peptide conjugation rescues poor immunogenicity of the HA stem

et al. 2020

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Influenza virus infection is a global public health threat. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. There is a critical need for developing “universal” vaccines that protect against all influenza viruses. HA stem is a promising target for developing broad-spectrum influenza vaccines due to its relatively conserved feature. However, HA stem is weakly immunogenic when administered alone in a soluble form. Several approaches have been employed to improve the immunogenicity of HA stem, including conjugation of HA stem with a highly immunogenic carrier protein or displaying HA stem on a nanoparticle scaffold. Converting a weakly immunologic protein into a multimer through aggregation can significantly enhance its immunogenicity, with some multimeric protein aggregates previously shown to be more immunogenic than their soluble counterparts in animal models. Here, we show that a chemically coupling a peptide derived from the head domain of PR8 HA (P35) with the poorly immunogenic HA stem protein results in aggregation of the HA stem which significantly increases stem-specific B cell responses following vaccination. Importantly, vaccination with this conjugate in the absence of adjuvant still induced robust B cell responses against stem in vivo. Improving HA stem immunogenicity by aggregation provides an alternative avenue to conjugation with exotic carrier proteins or nanoparticle formulation.

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Tracking progress in universal influenza vaccine development

Cited by 19 publications

References 25 publications

Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

Animal Models Utilized for the Development of Influenza Virus Vaccines

Aggregation by peptide conjugation rescues poor immunogenicity of the HA stem

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