Evaluation of Next-Generation H3 Influenza Vaccines in Ferrets Pre-Immune to Historical H3N2 Viruses
James D. Allen,Ted M. Ross +1 more
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This paper examined the role that pre-existing immunity plays on influenza virus vaccination and found that vaccines with the H3 COBRA HA antigens had more cross-reactive antibodies following a single vaccination in all three pre-immune regimens than vaccines with WT H3 HA vaccine comparators against historical, contemporary and future drifted A(H3N2) influenza viruses.Abstract:
Each person has a unique immune history to past influenza virus infections. Exposure to influenza viruses early in life establishes memory B cell populations that influence future immune responses to influenza vaccination. Current influenza vaccines elicit antibodies that are typically strain specific and do not offer broad protection against antigenically drifted influenza strains in all age groups of people. This is particularly true for vaccine antigens of the A(H3N2) influenza virus subtype, where continual antigenic drift necessitates frequent vaccine reformulation. Broadly-reactive influenza virus vaccine antigens offer a solution to combat antigenic drift, but they also need to be equally effective in all populations, regardless of prior influenza virus exposure history. This study examined the role that pre-existing immunity plays on influenza virus vaccination. Ferrets were infected with historical A(H3N2) influenza viruses isolated from either the 1970's, 1980's, or 1990's and then vaccinated with computationally optimized broadly reactive antigens (COBRA) or wild-type (WT) influenza virus like particles (VLPs) expressing hemagglutinin (HA) vaccine antigens to examine the expansion of immune breadth. Vaccines with the H3 COBRA HA antigens had more cross-reactive antibodies following a single vaccination in all three pre-immune regimens than vaccines with WT H3 HA antigens against historical, contemporary, and future drifted A(H3N2) influenza viruses. The H3 COBRA HA vaccines also induced antibodies capable of neutralizing live virus infections against modern drifted A(H3N2) strains at higher titers than the WT H3 HA vaccine comparators.read more
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Bivalent H1 and H3 COBRA Recombinant Hemagglutinin Vaccines Elicit Seroprotective Antibodies against H1N1 and H3N2 Influenza Viruses from 2009 to 2019
James D. Allen,Ted M. Ross +1 more
TL;DR: Overall, the newly generated COBRA HA antigens had the ability to induce broadly reactive antibodies in influenza-naive and preimmune animals in both monovalent and bivalent formulations, and these antIGens outperformed H1 and H3 WT rHA vaccine antigen by eliciting seroprotective antibodies against panels of antigenically drifted historical H1N1 andH3N2 vaccine strains from 2009 to 2019.
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Influenza and Universal Vaccine Research in China
TL;DR: Wang et al. as mentioned in this paper analyzed cases related to influenza virus infection and death in China in recent years, and summarized the candidate immunogens designed based on the structure of influenza virus, hoping to provide ideas for the design and development of new influenza vaccines in the future.
Journal ArticleDOI
Differential Recognition of Computationally Optimized H3 Hemagglutinin Influenza Vaccine Candidates by Human Antibodies
TL;DR: Overall, these studies determined that COBRA H3 HA proteins have correct antigenic and structural features, and the proteins are recognized by B cells and monoclonal antibodies isolated from seasonally vaccinated humans.
Journal ArticleDOI
Ferret model to mimic the sequential exposure of humans to historical H3N2 influenza viruses.
Shiho Chiba,Masato Hatta,David J. Pattinson,Atsuhiro Yasuhara,Gabriele Neumann,Yoshihiro Kawaoka +5 more
TL;DR: In this paper , the authors describe a ferret model to mimic the serial exposure of humans to antigenically different historical H3HA proteins and demonstrate that sequential exposure to antigenally different HAs elicits broader neutralizing activity in sera and enhances immune responses against more antigenically distinct viruses.
Posted ContentDOI
Differential recognition of computationally optimized H3 hemagglutinin influenza vaccine candidates by human antibodies
TL;DR: In this paper , the structural integrity of an H3N2 COBRA HAs, namely TJ5 and J4, was determined via a 3.4 Å structure via cryo-electron microscopy.
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New low-viscosity overlay medium for viral plaque assays
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Journal ArticleDOI
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