Serum Samples From Middle-aged Adults Vaccinated Annually with Seasonal Influenza Vaccines Cross-neutralize Some Potential Pandemic Influenza Viruses

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Abstract

We examined serum samples from adults ages 48–64 who received multiple seasonal influenza vaccines from 2004 to 2009 for cross-neutralizing antibodies to potential pandemic strains. Using pseudoviruses bearing various hemagglutinins (HA-pseudoviruses), we found serum neutralization titers (≥160) in 100% against A/Japan/305/1957 (H2N2), 53% against A/Hong Kong/1073/99 (H9N2), 56% against the H3N2 variant A/Indiana/08/11 (H3N2v), 11% against A/Hong Kong/G9/97 (H9N2), and 36% A/chicken/Hong Kong/SF4/01 (H6N1). None had titers >160 to A/Shanghai/2/13 (H7N9) or A/Netherlands/219/03 (H7N7). Thirty-six percent to 0% had neutralization titers to various H5N1 strains. Titers to H9, H6, and H5 HA-pseudoviruses correlated with each other, but not with H3N2v, suggesting group-specific cross-neutralization.

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Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

Kathy Hancock, Vic Veguilla, Xiuhua Lu … (2009)

A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies. 2009 Massachusetts Medical Society

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Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine.

Davide Corti, Amorsolo L Suguitan, Debora Pinna … (2010)

The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1-H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine. Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA. By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate. The mAbs used different VH genes and carried a high frequency of somatic mutations. With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid-sensitive epitopes in the HA stem region. Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes. These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.

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Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v).

Vladimir Gilca, Naveed Janjua, Marc Dionne … (2012)

Cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States, primarily among children. We estimate levels of cross-reactive antibody to H3N2v by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV), with or without adjuvant, may increase seroprotection. Antibody to H3N2v was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by microneutralization assay. Seroprevalence and seroprotection were defined as an HI titer of ≥40, and levels were compared with those for ancestral and contemporary human strains. The analysis included 1116 sera collected during fall 2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced antibody levels were also assessed in sera from 136 children aged <10 years and 65 adults aged 20-59 years before and after receipt of 2010-2011 split TIV and in sera from 182 elderly individuals aged ≥65 years before and after receipt of 2011-2012 split TIV (for 31 individuals), MF59-adjuvanted TIV (for 72), or unadjuvanted subunit TIV (for 79). The overall prevalence of HI titers of ≥40 against A(H3N2)v was 25%. No children aged <5 years and <20% of individuals aged ≤14 years or ≥40 years had an HI titer of ≥40. Conversely, among individuals aged 15-39 years, half of teens and adults showed H3N2v seroprotection. Following TIV receipt, <15% of individuals in any vaccine group developed a 4-fold increase in antibody level. A substantial proportion of adolescents and young adults have cross-reactive antibody against emerging H3N2v, whereas children and older adults show broad susceptibility. Recent formulations of TIV do not substantially increase seroprotection. A specific vaccine would be needed if H3N2v establishes epidemic spread. NCT01140009 and NCT01368796.

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Author and article information

Journal

Journal ID (nlm-ta): J Infect Dis

Journal ID (iso-abbrev): J. Infect. Dis

Journal ID (publisher-id): jid

Journal ID (hwp): jinfdis

Title: The Journal of Infectious Diseases

Publisher: Oxford University Press

ISSN (Print): 0022-1899

ISSN (Electronic): 1537-6613

Publication date (Print): 01 February 2016

Publication date (Electronic): 04 August 2015

Volume: 213

Issue: 3

Pages: 403-406

Affiliations

[1 ] Laboratory of Immunoregulation, Division of Viral Products

[2 ] Division of Hematology, Center for Biologics Evaluation and Research, US Food and Drug Administration , Silver Spring, Maryland

Author notes

Correspondence: C. D. Weiss, Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, WO Bldg 72, Rm 1214, Silver Spring, MD 20993 ( carol.weiss@ 123456fda.hhs.gov ).

Article

Publisher ID: jiv407

DOI: 10.1093/infdis/jiv407

PMC ID: 7313900

PubMed ID: 26243315

SO-VID: 62ca908d-ccfe-485d-a3c5-92a55caa38c8

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This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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Date received : 6 May 2015

Date accepted : 22 July 2015

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Serum Samples From Middle-aged Adults Vaccinated Annually with Seasonal Influenza Vaccines Cross-neutralize Some Potential Pandemic Influenza Viruses

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Abstract

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Vaccines

Most cited references 9

Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine.

Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v).

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