Intranasal immunization of mice with herpes simplex virus type 2 recombinant gD2: the effect of adjuvants on mucosal and serum antibody responses

Abstract

SUMMARYMucosal immunization offers the potential for inducing IgA antibody responses in the vagina, the site of infection for many viruses, including herpes simplex type 2 (HSV-2). To investigate this possibility, mice were immunized intranasally with 10 mg glycoprotein D2 (gD2) from HSV combined with a series of adjuvants of proven efficacy; the oil in water emulsion MF59, poly(,-lactide-co-glycolide) microparticles (PLG) (encapsulated or co-administered ), immune-stimulating complexes (iscoms) (incorporated or co-administered with iscomatrix) and the genetically detoxified enterotoxin from Escherichia coli, LT-K63. Encapsulation of gD2 into PLG microparticles, incorporation of gD2 into iscoms and co-administration of gD2 with LT-K63 induced mucosal IgA antibody responses (nasal wash, saliva and vaginal wash) which were greater than those induced by intramuscular administration of gD2 with MF59. Intranasal immunization with these formulations also induced substantial levels of serum IgG and neutralizing antibodies. These studies demonstrated that intranasal immunization with potent adjuvants is an effective means to induce mucosal antibody responses, even in the lower genital tract.

Trachea, Lung, and Tracheobronchial Lymph Nodes Are the Major Sites Where Antigen-Presenting Cells Are Detected after Nasal Vaccination of Mice with Human Papillomavirus Type 16 Virus-Like Particles

“…The efficiency of a prophylactic vaccine against HPV16 relies on the ability to induce a neutralizing immune response in genital secretions. Many reports suggested the importance of the NALT in the induction of a specific mucosal immune response after intranasal immunization (11,18,46,49). However, we have previously shown that nasal vaccination with low doses of HPV16 VLP was inefficient if the antigen did not contact the lung of the mice (4).…”

Herpes Simplex Virus Type 2 Vaccines: New Ground for Optimism?

“…They also reduced the symptoms of vaginal HSV-2 infection in guinea pigs (63,70,88). Glycoproteins gD and/or gB prepared from infected cells or constructed by recombinant methods reduced HSV-2 disease in animal models (16,23,74,97,105), modestly decreased the frequency and severity of recurrences, and reduced the incidence of virus shedding, but only when given together with potent adjuvants (46,79). The adjuvant effect was also strong in vaccination by the mucosal route (37).…”

Characterization of Human Immunodeficiency Virus Gag-Specific Gamma Interferon-Expressing Cells following Protective Mucosal Immunization with Alphavirus Replicon Particles

“…Intranasal (i.n.) immunization induces local immunity, not only in the nasally associated lymphoid tissue and the lung but also in the female genital tract, in rodents (1,14,31,53,61) as well as humans and nonhuman primates (3,20,34,44). Similarly, intravaginal (IVAG) and intrarectal immunization of rodents also induces local immunity in the genital tract.…”