Cell-Mediated Immunity Against Antigenically Drifted Influenza A(H3N2) Viruses in Children During a Vaccine Mismatch Season

Kim, Jin Hyang; Mishina, Margarita; Chung, Jessie R.; Cole, Kelly Stefano; Nowalk, Mary Patricia; Martin, Judith M.; Spencer, Sarah; Flannery, Brendan; Zimmerman, Richard K.; Sambhara, Suryaprakash

doi:10.1093/infdis/jiw311

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…Interestingly, the breadth of HAI activity was enhanced to include antigenically distinct H1N1 viruses, such as the swine-like pandemic H1N1 CA/09 virus, using combinations of seasonal viruses that circulated between 2 and 23 years in the past. These data are supported by the report that broadly cross-reactive immunity, conferred by prior infection, may be directly responsible for the enhanced efficacy of antigenically related, as well as distant, vaccine strains (34). Comparing the breadth of elicited antibody HAI activity, we predict that the elicitation of broad HAI activity against antigenically distinct H1N1 viruses from the past will be predictive of protection against antigenically distinct future strains.…”

Section: Discussionsupporting

confidence: 74%

Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

Carter

Darby

Johnson

et al. 2017

J Virol

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Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long-lasting protective immune responses. The goal of these vaccines is to stimulate immune responses that react against most, if not all, circulating influenza strains, over a long period of time in all populations of people. Commonly, these experimental vaccines are tested in naive animal models that do not have anti-influenza immune responses; however, humans have preexisting immunity to influenza viral antigens, particularly antibodies to the HA and NA glycoproteins. Therefore, this study investigated how preexisting antibodies to historical influenza viruses influenced HAI-specific antibodies and protective efficacy using a broadly protective vaccine candidate.

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Section: Discussionsupporting

confidence: 74%

Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

Carter

Darby

Johnson

et al. 2017

J Virol

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“…[ 7 ] A recent study reconfirmed that the amount of preexisting serum antibodies negatively correlated with the response of influenza-specific memory B-cells to IIV among previously vaccinated children aged 3 to 17 years. [ 13 ]…”

Section: Discussionmentioning

confidence: 99%

“…As the results of the studies, the amount of drifted antigen-specific IgG-secreting cells was strongly correlated with that of vaccine antigen-specific IgG-secreting cells (correlation coefficient: 0.82), the geometric mean fold rise of drifted antigen-specific antibody titers was comparable with that of vaccine antigen-specific antibody titers, although the pre- and postvaccination GMTs of drifted antigen-specific antibodies were 10-fold lower than the those of the vaccine antigen-specific antibodies, in terms of microneutralization titer. [ 13 , 15 ] As the cross-reactivities of antibodies may vary depending on the age of vaccinees and the profile of antigens, further studies are needed to understand properly the cross-reactivities of antibodies induced by IIV especially in young children.…”

Section: Discussionmentioning

confidence: 99%

Prior vaccinations improve immunogenicity of inactivated influenza vaccine in young children aged 6 months to 3 years

et al. 2018

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“…Elevated antibody titers to IIV are correlated with upregulation of B-cell specific transcripts, upregulation of immunoglobulin genes, and proliferation-associated genes. These responses may be predictors of vaccine-specific antibody and plasmablast responses at seven days post vaccination [15], as Kim et al have shown a similar relationship between antibody titers and circulating plasmablasts following IIV vaccination [16]. More recently, a methodology has been described for isolating and characterizing RNA transcripts in peripheral blood cell subsets compared to whole blood following influenza vaccination [17].…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression elicited by children in response to the 2015–16 live attenuated versus inactivated influenza vaccine

Cole

Martin

Horne

et al. 2017

Vaccine

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Background In recent influenza seasons, the live attenuated influenza vaccine (LAIV) has not demonstrated the same level of vaccine effectiveness as that observed among children who received the inactivated influenza vaccine (IIV). To better understand this difference, this study compared the mRNA sequencing transcription profile (RNA seq) in children who received either IIV or LAIV. Methods Children 3–17 years of age receiving quadrivalent influenza vaccine were enrolled. Blood samples were collected on Day 0 prior to vaccination and again on Day 7 (range 6–10 days) following vaccination. Total RNA was isolated from PAXgene tubes and sequenced for a custom panel of 89 transcripts using the TruSeq Targeted RNA Expression method. Fold differences in normalized RNA seq counts from Day 0 to Day 7 were calculated, log2 transformed and compared between the two vaccine groups. Results Of 72 children, 46 received IIV and 26 received LAIV. Following IIV vaccination, 7 genes demonstrated significant differential expression at Day 7 (down-regulated). In contrast, following LAIV vaccination, 8 genes demonstrated significant differential expression at Day 7 (5 up-regulated and 3 down-regulated). Only two genes demonstrated similar patterns of regulation in both groups. Conclusions Differential regulation of genes was observed between 2015–16 LAIV and IIV recipients. These results help to elucidate the immune response to influenza vaccines and may be related to the difference in vaccine effectiveness observed in recent years between LAIV and IIV.

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Cell-Mediated Immunity Against Antigenically Drifted Influenza A(H3N2) Viruses in Children During a Vaccine Mismatch Season

Cited by 9 publications

References 34 publications

Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

Prior vaccinations improve immunogenicity of inactivated influenza vaccine in young children aged 6 months to 3 years

Differential gene expression elicited by children in response to the 2015–16 live attenuated versus inactivated influenza vaccine

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