TY - JOUR
T1 - 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
T2 - A Randomised Trial
AU - Bethell, Delia
AU - Saunders, David
AU - Jongkaewwattana, Anan
AU - Kramyu, Jarin
AU - Thitithayanont, Arunee
AU - Wiboon-ut, Suwimon
AU - Yongvanitchit, Kosol
AU - Limsalakpetch, Amporn
AU - Kum-Arb, Utaiwan
AU - Uthaimongkol, Nichapat
AU - Garcia, Jean Michel
AU - Timmermans, Ans E.
AU - Peiris, Malik
AU - Thomas, Stephen
AU - Engering, Anneke
AU - Jarman, Richard G.
AU - Mongkolsirichaikul, Duangrat
AU - Mason, Carl
AU - Khemnu, Nuanpan
AU - Tyner, Stuart D.
AU - Fukuda, Mark M.
AU - Walsh, Douglas S.
AU - Pichyangkul, Sathit
N1 - Funding Information:
The authors declare they have no competing interests. This study was supported by MedImmune, which also provided FluMist Seasonal Trivalent Live Attenuated Intranasal Vaccine for use in the trial. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. There are no patents, products in development or marketed products to declare.
PY - 2013/3/26
Y1 - 2013/3/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875448994&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0059674
DO - 10.1371/journal.pone.0059674
M3 - Article
C2 - 23555741
AN - SCOPUS:84875448994
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e59674
ER -