Publication: Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial
Issued Date
2013-03-26
Resource Type
ISSN
19326203
Other identifier(s)
2-s2.0-84875448994
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE. Vol.8, No.3 (2013)
Suggested Citation
Delia Bethell, David Saunders, Anan Jongkaewwattana, Jarin Kramyu, Arunee Thitithayanont, Suwimon Wiboon-ut, Kosol Yongvanitchit, Amporn Limsalakpetch, Utaiwan Kum-Arb, Nichapat Uthaimongkol, Jean Michel Garcia, Ans E. Timmermans, Malik Peiris, Stephen Thomas, Anneke Engering, Richard G. Jarman, Duangrat Mongkolsirichaikul, Carl Mason, Nuanpan Khemnu, Stuart D. Tyner, Mark M. Fukuda, Douglas S. Walsh, Sathit Pichyangkul Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial. PLoS ONE. Vol.8, No.3 (2013). doi:10.1371/journal.pone.0059674 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/31048
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial
Author(s)
Delia Bethell
David Saunders
Anan Jongkaewwattana
Jarin Kramyu
Arunee Thitithayanont
Suwimon Wiboon-ut
Kosol Yongvanitchit
Amporn Limsalakpetch
Utaiwan Kum-Arb
Nichapat Uthaimongkol
Jean Michel Garcia
Ans E. Timmermans
Malik Peiris
Stephen Thomas
Anneke Engering
Richard G. Jarman
Duangrat Mongkolsirichaikul
Carl Mason
Nuanpan Khemnu
Stuart D. Tyner
Mark M. Fukuda
Douglas S. Walsh
Sathit Pichyangkul
David Saunders
Anan Jongkaewwattana
Jarin Kramyu
Arunee Thitithayanont
Suwimon Wiboon-ut
Kosol Yongvanitchit
Amporn Limsalakpetch
Utaiwan Kum-Arb
Nichapat Uthaimongkol
Jean Michel Garcia
Ans E. Timmermans
Malik Peiris
Stephen Thomas
Anneke Engering
Richard G. Jarman
Duangrat Mongkolsirichaikul
Carl Mason
Nuanpan Khemnu
Stuart D. Tyner
Mark M. Fukuda
Douglas S. Walsh
Sathit Pichyangkul
Abstract
Introduction: Recent studies have demonstrated that inactivated seasonal influenza vaccines (IIV) may elicit production of heterosubtypic antibodies, which can neutralize avian H5N1 virus in a small proportion of subjects. We hypothesized that prime boost regimens of live and inactivated trivalent seasonal influenza vaccines (LAIV and IIV) would enhance production of heterosubtypic immunity and provide evidence of cross-protection against other influenza viruses. Methods: In an open-label study, 26 adult volunteers were randomized to receive one of four vaccine regimens containing two doses of 2009-10 seasonal influenza vaccines administered 8 (±1) weeks apart: 2 doses of LAIV; 2 doses of IIV; LAIV then IIV; IIV then LAIV. Humoral immunity assays for avian H5N1, 2009 pandemic H1N1 (pH1N1), and seasonal vaccine strains were performed on blood collected pre-vaccine and 2 and 4 weeks later. The percentage of cytokine-producing T-cells was compared with baseline 14 days after each dose. Results: Subjects receiving IIV had prompt serological responses to vaccine strains. Two subjects receiving heterologous prime boost regimens had enhanced haemagglutination inhibition (HI) and neutralization (NT) titres against pH1N1, and one subject against avian H5N1; all three had pre-existing cross-reactive antibodies detected at baseline. Significantly elevated titres to H5N1 and pH1N1 by neuraminidase inhibition (NI) assay were observed following LAIV-IIV administration. Both vaccines elicited cross-reactive CD4+ T-cell responses to nucleoprotein of avian H5N1 and pH1N1. All regimens were safe and well tolerated. Conclusion: Neither homologous nor heterologous prime boost immunization enhanced serum HI and NT titres to 2009 pH1N1 or avian H5N1 compared to single dose vaccine. However heterologous prime-boost vaccination did lead to in vitro evidence of cross-reactivity by NI; the significance of this finding is unclear. These data support the strategy of administering single dose trivalent seasonal influenza vaccine at the outset of an influenza pandemic while a specific vaccine is being developed. Trial Registration: ClinicalTrials.gov NCT01044095. © 2013 Bethell, et al.