Humoral and Cell-Mediated Immunity to Pandemic H1N1 Influenza in a Canadian Cohort One Year Post-Pandemic: Implications for Vaccination

Lisa E Wagar,Brian J Ward,Beth Lowcock,Julie Foisy,Paulina C Drohomyrecky,Anu Rebbapragada,Camille Achonu,Laura Rosella,Jonathan Gubbay,Anne-Luise Winter,Tania H Watts,Natasha Crowcroft

doi:10.1371/journal.pone.0028063

Lisa E Wagar, Brian J Ward + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0028063

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Abstract

We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105) of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity.

Highlights

A novel swine-origin H1N1 influenza virus emerged in North America in mid-April of 2009, resulting in widespread infection [1,2]
T cells produced against pH1N1 2009 are able to respond to challenge with the 1918 pandemic H1N1 strain [10] and memory T cells generated against past seasonal infections can respond to pH1N1 challenge [11,12,13], suggesting that T cell cross-reactivity exists in primed hosts
By analyzing the product of the median fluorescence intensity (MFI) and the frequency of T cells with IFNc staining, the response value reported takes into account both the proportion of cells responding to influenza virus and the amount of IFNc per cell

Summary

Introduction

A novel swine-origin H1N1 influenza virus (pH1N1) emerged in North America in mid-April of 2009, resulting in widespread infection [1,2]. Infection in older age groups resulted in more severe illness and increased mortality rates compared to the general population [3,5,6]. It has been suggested that older people who had been exposed to an H1N1 influenza from the early 20th century may have been protected by pre-existing cross-reactive antibodies [7,8], as strains originating from the 1918 pandemic are antigenically similar to the 2009 strain [9]. T cells produced against pH1N1 2009 are able to respond to challenge with the 1918 pandemic H1N1 strain [10] and memory T cells generated against past seasonal infections can respond to pH1N1 challenge [11,12,13], suggesting that T cell cross-reactivity exists in primed hosts.

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