Induction in Mucosa of IgG and IgA Antibodies against Parenterally Administered Soluble Immunogens

Abstract

The induction of a mucosal immunity provides an additional principle of vaccination by preventing the entry of pathogens in the body. Albeit the fact that intensive research has been conducted on local vaccines, the major mucosal vaccine commercially available for human use remains the oral polio vaccine. We have previously demonstrated that parenteral vaccination in humans with tetanus toxoid (TT) results in a genital immunoglobulin (Ig)G antibody (Ab) response. Here, we show that injections of TT with no adjuvant induces an anti-TT response in the mucosal tissues of normal BALB/c mice. The response is multiregional, involves both IgG and IgA isotypes, and is long-lasting. Similarly, injections of haptens coupled to TT or to other diffusible proteins may induce mucosal Abs. These results led us to immunize normal BALB/c mice with a viral peptide coupled to TT by disulfide bridging. The hapten was a 17 amino acid peptide containing the ELDKWA sequence of human immunodeficiency virus (HIV)-1 gp41. A significant IgG and IgA Ab response to the immunizing peptide was induced in various mucosal tissues despite the presence of a suboptimal Ab response in the spleen. The results indicate that mucosal immunity to peptides that are candidates for human vaccinations may be achieved by parenteral adjuvant-free immunization with peptide coupled to TT. Dr J.-P. Bouvet, INSERM U430, Ho Ãpital Broussais,

Impairment by Mucosal Adjuvants and Cross-Reactivity with Variant Peptides of the Mucosal Immunity Induced by Injection of the Fusion Peptide PADRE-ELDKWA

“…injection of a synthetic fusion peptide containing ELDKWA and PADRE (12). Interestingly, we showed that this mucosal immune response persists for a long time after the booster injection (11,12).…”

“…Therefore, most research programs deal with persisting Ags, such as live vaccines (6). Nonetheless, our previous results showed that a mucosal Ab response may persist for as long as 8 months following immunization of mice by injection of a soluble Ag, such as tetanus toxoid (11).…”

“…Our group has induced both systemic and mucosal immune responses following i.m. injection of mice with a 17-aa peptide (EKNEQELLELDKWASLWN) coupled with tetanus toxoid (11). Recently, we obtained an Ab response in the mucosal organs by i.m.…”

Heteropentameric Cholera Toxin B Subunit Chimeric Molecules Genetically Fused to a Vaccine Antigen Induce Systemic and Mucosal Immune Responses: a Potential New Strategy To Target Recombinant Vaccine Antigens to Mucosal Immune Systems

“…Having a similar mechanism of protein secretion for yeast and mammalian cells, heteropentameric constructs may have advantages over homopentamers or holotoxin-like molecules; their secretory nature may increase cellular uptake of the fusion chimera by adjacent cells or by the professional antigen-presenting cells for increased major histocompatibility complex class I and/or class II presentation to elicit enhanced humoral as well as cellular immune responses (possibly including mucosal responses) (7,28).…”

Parenteral Vaccination Can Be an Effective Means of Inducing Protective Mucosal Responses

“…Studies using murine or other small-laboratory-animal models have also provided relevant, although at times inconclusive, evidence of mucosally committed responses after parenteral delivery of vaccines (11)(12)(13)(14)(15). A few important examples include reports of long-lasting mucosal IgA responses in intestinal tissues of BALB/c mice after intramuscular injection of nonadjuvanted tetanus toxoid (TT) and persistent levels of intestinal and vaginal antibodies after intramuscular immunization of mice with an HIV gp41 peptide mixed with a major histocompatibility complex class II (MHC-II) binding peptide.…”