Baculovirus as an avian influenza vaccine vector: Differential immune responses elicited by different vector forms

Baculovirus is an enveloped virus that infects insects in nature and has emerged as a novel vaccine vector. We previously constructed a recombinant baculovirus displaying the hemagglutinin protein (HA) of avian influenza virus (AIV) on the viral envelope (Bac-HA64), and demonstrated the induction of humoral responses in immunized mice. To improve the vector design and explore how the vector forms influence the vaccine efficacy, we constructed two more baculoviruses Bac-CHA and Bac-CHA/HA64. Bac-CHA expressed HA after transducing the host cells while Bac-CHA/HA64 not only expressed HA but also displayed HA on the envelope. After administration into BALB/c mice, all three vectors elicited HA-specific humoral (IgG1, IgG2a and hemagglutination inhibition titers), mucosal (IgA titers) and cellular (interferon (IFN)-γ and IL-4 producing T cells and IFN-γ+/CD8+ T cells) immune responses. Intriguingly, the magnitudes and types of responses hinged on the vaccine form and administration route. Via intranasal (i.n.) and subcutaneous (s.c.) inoculation, the HA-displaying vectors Bac-HA64 and Bac-CHA/HA64 triggered stronger humoral and mucosal responses than Bac-CHA, but upon intramuscular (i.m.) injection the HA-expressing vectors (Bac-CHA and Bac-CHA/2HA64) elicited more robust humoral and cellular responses than Bac-HA64. Via either administration route, the dual form vaccine Bac-CHA/HA64 gave rise to superior or at least comparable HA-specific immune responses than the other two vaccine forms, implicating the potential of Bac-CHA/HA64 as a vaccine candidate against AIV infection.