Intranasal immunization of baculovirus displayed hemagglutinin confers complete protection against mouse adapted highly pathogenic H7N7 reassortant influenza virus.

BACKGROUND: Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA). The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n.) or subcutaneously (s.c.) with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs. CONCLUSION: Our results indicated that protection from high pathogenic H7N7 (NL/219/03) virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections.

Effective intranasal therapeutics and prophylactics with monoclonal antibody against lethal infection of H7N7 influenza virus.

Recurrence of highly pathogenic avian influenza (HPAI) virus subtype H7 in humans and poultry continues to be a serious concern to public health. No effective prevention and treatment are currently available against H7 infection. One H7 monoclonal antibody, Mab 62 was selected and characterized. Mab 62 presented efficient neutralization activity against all six representative H7 strains tested, including the H7N9 strain from the recent outbreak in China. The epitope of 62 identified on H7 HA1 exists in all the human H7 strains, including the recent H7N9 strains from China. Mab 62 when administered passively, pre or post challenge with 5 MLD50 (50% mouse lethal dose) HPAI H7N7 influenza viruses could protect 100% of the mice from death. The efficacy of intranasal administration of the Mab was evaluated versus the intraperitoneal route. In the therapeutic study, body weight loss and virus load were reduced in intranasally inoculated mice, as compared to the intraperitoneal group. Intranasal administration results in early clearance of the virus from the lungs and completely prevents lung pathology of H7N7. The study confirmed that intranasal administration of Mab 62 is either an effective prophylactic or therapeutic means against H7 lethal infection. The results of epitope analysis suggest the potential of Mab 62 to be used for the efficacious prevention and treatment against the recent human H7N9 strains.