Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine

He, Xiaosong; Sasaki, Sanae; Baer, Jane; Khurana, Surender; Golding, Hana; Treanor, John J.; Topham, David J.; Sangster, Mark Y.; Jin, Hong; Dekker, Cornelia L.; Subbarao, Kanta; Greenberg, Harry B.

doi:10.1093/infdis/jis664

Cited by 23 publications

(25 citation statements)

References 28 publications

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“…Recent studies demonstrated that infection or vaccination with the 2009 pH1N1 virus favors induction of broadly cross-reactive HA-specific Abs, including Abs reactive with the HA stalk (14)(15)(16)(17)(18). Importantly, our analysis adds to the limited available information on circulating levels of stalk-reactive Abs before and after pH1N1 exposure.…”

Section: Discussionmentioning

confidence: 87%

“…The amount of Ab secreted by an individual ASC is approximately the same in young and elderly subjects (31). There is evidence that ASCs induced by pH1N1 vaccination produce higher-affinity HA head-reactive Abs in older subjects (13,16), but this difference probably diminishes with affinity maturation of the response in the younger subjects. Overall, it is likely that the difference between age cohorts in the relationship between the ASC frequency and HAI fold increase primarily reflects a numerically greater ASC response to vaccination in the young cohort.…”

Section: Discussionmentioning

confidence: 99%

“…This contrasted with the largely strain-specific Ab response to seasonal influenza vaccination (16,18,19). In models proposed to explain these observations (14)(15)(16), the Ab response to the seasonal vaccine largely reflects activation of abundant memory B cells that recognize immunodominant (and variable) epitopes in the HA head. The lower number of memory B cells specific for conserved epitopes in the HA head and stem are outcompeted when the antigen is limiting, and they do not contribute to the response.…”

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confidence: 98%

“…In recent studies, pH1N1 vaccination preferentially induced broadly cross-reactive Abs, including HA head-reactive Abs that neutralized a range of H1N1 strains and HA stalk-reactive Abs with neutralizing activity against viruses of different subtypes (14)(15)(16)(17). This contrasted with the largely strain-specific Ab response to seasonal influenza vaccination (16,18,19).…”

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confidence: 99%

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B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

Sangster

Baer

Santiago

et al. 2013

Clin Vaccine Immunol

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The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and >70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virusspecific antibody (Ab)-secreting cells and >4-fold increases in HAI and MN titers. However, the response was strongest in the 18-to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18-to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the antiBrisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

Sangster

Baer

Santiago

et al. 2013

Clin Vaccine Immunol

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“…The exclusion is the pandemic virus H1N1pdm09: in that case, the generation of the cross-reactive antibodies directed to the subunit HA2 conservative sites after the disease and vaccination was shown [54,55].…”

Section: The Main Approaches To the Creation Of A Universal Vaccinementioning

confidence: 99%

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2016

MIR journal

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Prevention and Control of Influenza Viruses

Kapoor

Dhama

2014

Insight Into Influenza Viruses of Animals and Humans

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Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine

Abstract: The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain.

Cited by 23 publications

References 28 publications

B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

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Prevention and Control of Influenza Viruses

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