Antibody Persistence and Booster Responses to Split-Virion H5N1 Avian Influenza Vaccine in Young and Elderly Adults

Rajeka Lazarus, Sarah Kelly, Matthew D Snape, Corinne Vandermeulen, Merryn Voysey, Karel Hoppenbrouwers, Annick Hens, Pierre Van Damme, Stephanie Pepin, Isabel Leroux-Roels, Geert Leroux-Roels, Andrew J Pollard, Rajeka Lazarus, Sarah Kelly, Matthew D Snape, Corinne Vandermeulen, Merryn Voysey, Karel Hoppenbrouwers, Annick Hens, Pierre Van Damme, Stephanie Pepin, Isabel Leroux-Roels, Geert Leroux-Roels, Andrew J Pollard

Abstract

Avian influenza continues to circulate and remains a global health threat not least because of the associated high mortality. In this study antibody persistence, booster vaccine response and cross-clade immune response between two influenza A(H5N1) vaccines were compared. Participants aged over 18-years who had previously been immunized with a clade 1, A/Vietnam vaccine were re-immunized at 6-months with 7.5 μg of the homologous strain or at 22-months with a clade 2, alum-adjuvanted, A/Indonesia vaccine. Blood sampled at 6, 15 and 22-months after the primary course was used to assess antibody persistence. Antibody concentrations 6-months after primary immunisation with either A/Vietnam vaccine 30 μg alum-adjuvanted vaccine or 7.5 μg dose vaccine were lower than 21-days after the primary course and waned further with time. Re-immunization with the clade 2, 30 μg alum-adjuvanted vaccine confirmed cross-clade reactogenicity. Antibody cross-reactivity between A(H5N1) clades suggests that in principle a prime-boost vaccination strategy may provide both early protection at the start of a pandemic and improved antibody responses to specific vaccination once available.

Trial registration: ClinicalTrials.gov NCT00415129.

Conflict of interest statement

SP is an employee of Sanofi Pasteur. AJP has previously conducted studies on behalf of Oxford University funded by vaccine manufacturers but no longer does so. AJP chairs the UK Department of Health’s (DH) Joint Committee on Vaccination and Immunisation (JCVI); the views expressed in this manuscript do not necessarily reflect the views of JCVI or DH. MDS has conducted clinical trials on behalf of Oxford University sponsored by vaccine manufacturers. MDS does not accept any personal payments from vaccine manufacturers: grants for support of educational activities are paid to an educational/administrative fund held by the Department of Paediatrics, Oxford University. RL and MDS have received financial assistance from vaccine manufacturers to attend scientific meetings. PVD acts as chief and principal investigator for vaccine trials conducted on behalf of the University of Antwerp, for which the University obtains research grants from vaccine manufacturers; speakers fees for presentations on vaccines are paid directly to an educational fund held by the University of Antwerp. CV acts as principal and sub-investigator for clinical trials conducted on behalf of the KU Leuven, for which the University obtains research grants; CV has received financial assistance from vaccine manufacturers to attend scientific meetings. Speakers fees for presentations on vaccines are paid to a charity fund held by the Department of Pediatrics, KU Leuven. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study CONSORT diagram.
Fig 1. Study CONSORT diagram.
NC: non compliance with protocol; SAE: serious adverse event; WD: voluntary withdrawal for unspecified reasons; LFU: lost to follow up.

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