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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 《PloS one》2013,8(3)
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相似文献2.
Ans Timmermans Melanie C. Melendrez Youry Se Ilin Chuang Nou Samon Nichapat Uthaimongkol Chonticha Klungthong Wudtichai Manasatienkij Butsaya Thaisomboonsuk Stuart D. Tyner Sareth Rith Viseth Srey Horm Richard G. Jarman Delia Bethell Nitima Chanarat Julie Pavlin Tippa Wongstitwilairoong Piyaporn Saingam But Sam El Mark M. Fukuda Sok Touch Ly Sovann Stefan Fernandez Philippe Buchy Lon Chanthap David Saunders 《PloS one》2016,11(3)
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