Historical H1N1 Influenza Virus Imprinting Increases Vaccination Efficacy by Influencing Antibody Longevity and Neutralization Activity in Ferrets

Francis, Magen E.; McNeil, Mara; Dawe, Nicholas; Foley, Mary K.; King, Morgan; Ross, Ted M.; Kelvin, Alyson A.

doi:10.20944/preprints201907.0246.v1

Cited by 8 publications

(1 citation statement)

References 46 publications

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“…Finally, a 'non preimmune' or 'naïve pre-immune' group was included as a control for the vaccines alone. An H2N2 pre-immune group was also included as a pseudo "positive control" group since previous studies have shown that imprinting ferrets with a specific subtype of influenza virus followed by vaccination with another antigenically distinct influenza virus of the same subtype induces expansive intra-subtype antibodies (29). Two antigenically distinct H2N2 avian influenza viruses were used to establish the H2N2 pre-immunity because of the restrains of housing ferrets infected with BSL3 human H2N2 influenza viruses in high level containment for several months.…”

Section: Introductionmentioning

confidence: 99%

Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Pre-Immune to Seasonal Influenza A Viruses

Reneer

Skarlupka

Jamieson

et al. 2021

Preprint

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Influenza vaccines have traditionally been tested in naïve mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of life. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this manuscript, previously described H2 computationally optimized broadly reactive antigen (COBRA) HA vaccines (Z1, Z5) were tested in influenza virus 'pre-immune' ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish pre-immunity. These pre-immune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or WT H2 HA recombinant proteins in a prime-boost regimen. A set of naïve pre-immune or non pre-immune ferrets were also vaccinated to control the effects of the multiple different pre-immune states. All ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with pre-existing immune responses influenced recombinant H2 HA elicited antibodies following vaccination as measured by HAI and classical neutralization assays. Having both H3N2 and H1N1 immunological memory, regardless of the order of exposure, significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock vaccinated ferrets. While the vast majority of the pre-immune ferrets were protected from both morbidity and mortality across all of the different pre-immune states, the Z1 COBRA HA vaccinated ferrets had significantly higher antibody titers and recognized the largest number H2 influenza viruses in a classical neutralization assay compared to the other H2 HA-based vaccines.

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Section: Introductionmentioning

confidence: 99%

Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Pre-Immune to Seasonal Influenza A Viruses

Reneer

Skarlupka

Jamieson

et al. 2021

Preprint

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Pre-existing immunity to influenza viruses through infection and/or vaccination leads to viral mutational signatures associated with unique immune responses during a subsequent infection

Rioux

Yourkowski

et al. 2022

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Our biggest challenge to reducing the burden of seasonal influenza is the constant antigen drift of circulating influenza viruses which then evades the protection of pre-existing immunity. Continual viral infection and influenza vaccination creates a layered immune history in people, however, how host preimmunity interacts with an antigenically divergent virus exposure is poorly understood. Here we investigated the influence of host immune histories on influenza viral mutations. Immune backgrounds were devised in mice similar to what is experienced in people: naive; previously infected (A/FM/1/1947); previously vaccinated (Sanofi quadrivalent vaccine); and previously infected and then vaccinated. Mice were challenged with the heterologous H1N1 strain A/Mexico/4108/2009 to assess protection, viral mutation, and host responses in respect to each immune background by RNAseq. Viral sequences were analyzed for antigenic changes using DiscoTope 2.0 and Immune Epitope Database (IEDB) Analysis Resource NetMHCpan EL 4.1 servers. The mock infected-vaccinated group consistently had the greatest number of viral mutations seen across several viral proteins, HA, NA, NP, and PB1 which was associated with strong antiviral responses and moderate T cell and B cell responses. In contrast, the preimmune-vaccinated mice were not associated with variant emergence and the host profiles were characterized by minimal antiviral immunity but strong T cell, B cell, and NK cell responses. This work suggests that the infection and vaccination history of the host dictates the capacity for viral mutation at infection through immune pressure. These results are important for developing next generation vaccination strategies.

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Does Vaccine-Induced Maternally-Derived Immunity Protect Swine Offspring against Influenza a Viruses? A Systematic Review and Meta-Analysis of Challenge Trials from 1990 to May 2021

Keay,

Poljak,

Alberts

et al. 2023

Animals

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It is unclear if piglets benefit from vaccination of sows against influenza. For the first time, methods of evidence-based medicine were applied to answer the question: “Does vaccine-induced maternally-derived immunity (MDI) protect swine offspring against influenza A viruses?”. Challenge trials were reviewed that were published from 1990 to April 2021 and measured at least one of six outcomes in MDI-positive versus MDI-negative offspring (hemagglutination inhibition (HI) titers, virus titers, time to begin and time to stop shedding, risk of infection, average daily gain (ADG), and coughing) (n = 15). Screening and extraction of study characteristics was conducted in duplicate by two reviewers, with data extraction and assessment for risk of bias performed by one. Homology was defined by the antigenic match of vaccine and challenge virus hemagglutinin epitopes. Results: Homologous, but not heterologous MDI, reduced virus titers in piglets. There was no difference, calculated as relative risks (RR), in infection incidence risk over the entire study period; however, infection hazard (instantaneous risk) was decreased in pigs with MDI (log HR = −0.64, 95% CI: −1.13, −0.15). Overall, pigs with MDI took about a ½ day longer to begin shedding virus post-challenge (MD = 0.51, 95% CI: 0.03, 0.99) but the hazard of infected pigs ceasing to shed was not different (log HR = 0.32, 95% CI: −0.29, 0.93). HI titers were synthesized qualitatively and although data on ADG and coughing was extracted, details were insufficient for conducting meta-analyses. Conclusion: Homology of vaccine strains with challenge viruses is an important consideration when assessing vaccine effectiveness. Herd viral dynamics are complex and may include concurrent or sequential exposures in the field. The practical significance of reduced weaned pig virus titers is, therefore, not known and evidence from challenge trials is insufficient to make inferences on the effects of MDI on incidence risk, time to begin or to cease shedding virus, coughing, and ADG. The applicability of evidence from single-strain challenge trials to field practices is limited. Despite the synthesis of six outcomes, challenge trial evidence does not support or refute vaccination of sows against influenza to protect piglets. Additional research is needed; controlled trials with multi-strain concurrent or sequential heterologous challenges have not been conducted, and sequential homologous exposure trials were rare. Consensus is also warranted on (1) the selection of core outcomes, (2) the sizing of trial populations to be reflective of field populations, (3) the reporting of antigenic characterization of vaccines, challenge viruses, and sow exposure history, and (4) on the collection of non-aggregated individual pig data.

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Historical H1N1 Influenza Virus Imprinting Increases Vaccination Efficacy by Influencing Antibody Longevity and Neutralization Activity in Ferrets

Cited by 8 publications

References 46 publications

Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Pre-Immune to Seasonal Influenza A Viruses

Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Pre-Immune to Seasonal Influenza A Viruses

Pre-existing immunity to influenza viruses through infection and/or vaccination leads to viral mutational signatures associated with unique immune responses during a subsequent infection

Does Vaccine-Induced Maternally-Derived Immunity Protect Swine Offspring against Influenza a Viruses? A Systematic Review and Meta-Analysis of Challenge Trials from 1990 to May 2021

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