Nasal or intramuscular immunization of mice with influenza subunit antigen and the B subunit of Escherichia coli heat-labile toxin induces IgA- or IgG-mediated protective mucosal immunity

Hydrophobic Inactivation of Influenza Viruses Confers Preservation of Viral Structure with Enhanced Immunogenicity

“…Serum antibody responses, a measure of immune protection for inactivated influenza virus vaccines, were similar between immunizations, with IgG titers from virus-infected animals being at most threefold greater than INA-inactivated X-31-immunized mice and HI titers being equivalent (Tables 1 and 2). At the same time, INA-inactivated X-31-immunized mice had increased mucosal IgA titers, which have been associated with enhanced homosubtypic and hetersubtypic protection (18,38,40). IgA antibodies are probably the major humoral contributor for the heterosubtypic protection observed in this study, although the effect of neutralizing IgG antibodies that are potent in vivo cannot be excluded.…”

“…Combined, this multifaceted immune response could not only provide improved protection to matched virus challenge but also improve immunity to heterosubtypic infection (13). In a variety of experimental models, subunit and particle-based vaccines with or without immune-stimulating compounds or adjuvants have provided heterosubtypic immunity; however, in most cases, these vaccination regimens utilize a prime-boost strategy with multiple immunizations (18,32,40). Here, we show that similar to live virus infection, a single intranasal immunization with INA-inactivated influenza virus provides protection against heterosubtypic challenge.…”

What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?

“…However, the requirement for mucosal immunization to generate protective "frontline immunity" against mucosal pathogens is highly controversial. On the one hand, numerous studies in the literature have demonstrated that immune responses are readily detectable at mucosal sites following systemic delivery of vaccines, and complete or partial protection from mucosal challenge is attainable (2,(33)(34)(35)(36)(37)(38)(39)(40). Systemic immunization is adequate for successful vaccines for some mucosal pathogens, notably the polio virus and the influenza virus, where high titers of neutralizing Abs are capable of clearing cellfree virus and preventing disease (34,41).…”

“…On the one hand, numerous studies in the literature have demonstrated that immune responses are readily detectable at mucosal sites following systemic delivery of vaccines, and complete or partial protection from mucosal challenge is attainable (2,(33)(34)(35)(36)(37)(38)(39)(40). Systemic immunization is adequate for successful vaccines for some mucosal pathogens, notably the polio virus and the influenza virus, where high titers of neutralizing Abs are capable of clearing cellfree virus and preventing disease (34,41). On the other hand, mucosal pathogens such as HIV-1, HPV, herpes viruses, Mycobacterium species, and other intracellular pathogens may require mucosal vaccine strategies that activate multiple arms of the innate and adaptive immune systems (29,30,(42)(43)(44)(45).…”

Phase I Evaluation of Intranasal Trivalent Inactivated Influenza Vaccine with Nontoxigenic Escherichia coli Enterotoxin and Novel Biovector as Mucosal Adjuvants, Using Adult Volunteers

“…One possibility is that this IgG reaches the mucosal lumen by transudation from the circulation (39), with studies of mice indicating that IgG antibodies are capable of providing protective mucosal immunity (12,21). In this regard, it seems important to elicit a strong mucosal IgG response to vaccination in order to achieve optimal virus neutralization at the portal of virus entry.…”