Paradee Teebumrung1, Karnyart Samnaun2, Alita Kongchanagul3, Kultida Jiamsomboon2 Punnee Pitisuttithum2,4, Pilaipan Puthavathana 5, Kobporn Boonnak1,2*
1Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
2 Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
3 Institute of Molecular Biosciences, Mahidol University, Nakhon Prathom, Thailand
4 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
5 Faculty of Medical Technology, Mahidol University, Thailand
The emergence of highly pathogenic avian influenza viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza virus infection. In this study, we investigated the safety and immunogenicity of an avian H5N2 lived attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. This study was conducted in two parts: part 1 was a randomized, double-blinded, placebo-controlled trial done over 18 months. We randomly assigned (2:1) healthy Thai adults aged 18-49 years to receive either two intranasal doses (0.25 mL per nostril) of LAIV H5N2 (101 participants) or placebo (51 participants) 21 days apart; in part 2, an open-labelled trial was done, in which previously vaccinated participants (40 from LAIV H5N2 group and 20 placebo) were given one intramuscular dose (0.5 mL) of inactivated H5N1 booster vaccine. The trials are registered with ClinicalTrial.gov, numbers NCT01841918 and NCT02229357. Our data showed that: (i) although two doses of LAIV H5N2 vaccine were poorly immunogenic as measured by hemagglutination inhibition assay, the priming effect of LAIV H5N2 was unmasked by boosting with H5N1 inactivated vaccine, (ii) the heterologous prime-boost vaccination enhanced hemagglutination inhibiting and virus neutralizing antibody responses against H5N1 viruses that are antigenically distinct from both vaccine strains, (iii) the prime-boost vaccination, which stimulated the immune system by administering a vaccine with different globular heads, but contains the same stalk domain of hemagglutinin protein, resulted in the stimulation of stalk antibody production in the volunteers who participated in this prime-boost trial. Although the specific immune mechanisms following prime-boost vaccination remains to be elucidated, our studies expand the option potentially available for eliciting robust responses to avian influenza vaccination in humans.