Superior cross‐protective effect of nasal vaccination to subcutaneous inoculation with influenza hemagglutinin vaccine

Abstract

Intranasal (i.n.) vs. subcutaneous (s.c.) administration of influenza hemagglutinin (HA) vaccine was systematically compared in BALB/c mice. Mice were immunized with different vaccines, together with cholera toxin B subunit as an adjuvant, and 4 weeks later were challenged with either a small (2 microliters) or a large (20 microliters) volume of mouse-adapted A/Guizhou-X (H3N2) virus, each of which gave virgin mice either a nasal or a lung predominant infection. Both i.n. and s.c. inoculations of A/Guizhou-X vaccine conferred almost complete protection against both challenges, i.n. inoculation of A/Fukuoka (H3N2) or A/Sichuan (H3N2) vaccine conferred almost complete cross-protection against 2-microliters challenge and a partial cross-protection against 20-microliters challenge, whereas the s.c. inoculation conferred no cross-protection against 2-microliters challenge with a partial cross-protection against 20-microliters challenge. Moreover, i.n. immunization of PR8 (H1N1) vaccine gave a slight cross-protection against 2-microliters challenge, while the s.c. inoculation did not. The degree of protection was easily improved by i.n. inoculation of higher doses of vaccine, but not by the s.c. inoculation. In parallel with the protection, the i.n. vaccination produced a high level of cross-reacting IgA and IgG antibody to A/Guizhou-X HA in nasal and broncho-alveolar washes, while the s.c. vaccination produced the cross-reacting IgG antibody alone. Thus, i.n. inoculation with inactivated vaccines, which induces cross-reacting anti-HA IgA antibody as well as IgG antibody, is more effective than s.c. vaccination for providing cross-protection against drift viruses.

The adjuvant effect of a non‐toxic mutant of heat‐labile enterotoxin of Escherichia coli for the induction of measles virus‐specific CTL responses after intranasal co‐immunization with a synthetic peptide

“…However, the use of strong mucosal adjuvants such as cholera toxin (CT) and heat-labile enterotoxin (LT) was shown to be necessary for the induction of an effective immune response. 1,2,3 Both of the toxins are composed of two subunits, A and B. The A subunit is responsible for ADPribosylation of the GTP-binding protein that increases intracellular levels of adenosine 3Ј,5Ј-monophosphate (cAMP).…”

M cell-targeted DNA vaccination

“…immunization, used in our study, has proven to be an effective method for stimulating both upper and lower respiratory immunity (19)(20)(21)(22). Moreover, this method of immunization has the ability to elicit distal mucosal immunity be it mediated by humoral or cellular immunity.…”

Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

“…The advantages of nasal-inactivated vaccines over the current vaccines are as follows: (i) The nasal vaccine induces both S-IgA Ab (mainly responsible for preventing virus infection in the upper respiratory tract) and serum IgG Ab (mainly responsible for providing protection against serious illness due to infection in the lower respiratory tract) responses; (ii) nasal S-IgA Abs are not only reactive with homologous virus HA but are also highly crossreactive with variant viral HA, thereby providing protection and cross-protection against homologous and variant viruses, respectively, whereas serum-derived IgG Abs are less cross-reactive and less cross-protective. Thus, nasal-inactivated vaccines are expected to be more effective than parenteral vaccines when the immunogenicity of the vaccine virus strain is different from that of the epidemic virus strain; (iii) the nasalinactivated vaccine will alleviate the phenomenon of`o riginal antigenic sin'' more effectively than current parenteral and live attenuated vaccines (21)(22)(23)(24)(25)54,55); (iv) the nasal-inactivated vaccine (non-infectious preparation) is expected to be available for high-risk subjects; (v) since the vaccine is sprayed into the nasal cavity, there is no pain involved. This may increase the vaccination rate.…”