Antibody-mediated protection and the mucosal immune system of the genital tract: relevance to vaccine design

Abstract

Mucosal tissues of the genital tracts and the distal intestinal tract are portals of entry for infectious agents of sexually transmitted diseases, including HIV-1. Although the genital and intestinal tracts share a common embryologic origin and remain in anatomical proximity, these two sites display remarkably different immunologic features, including the levels, isotypes and molecular forms of immunoglobulins, and magnitudes and qualities of humoral and cellular immune responses. Thus, viral and bacterial infections of the genital tract or intravaginal immunizations induce, in the absence of mucosal adjuvants, minimal immune responses. Consequently, to induce relevant immune responses in the genital tract, alternative immunization routes have been explored, including systemic, intranasal, oral, or rectal immunization and their combinations. In limited studies performed in animals, systemic immunization with a subsequent mucosal (intranasal) immunization proved to be effective in the induction of humoral immune responses in genital tract secretions. The approaches have been explored to a limited extent in humans.

An Attenuated Duck Plague Virus (DPV) Vaccine Induces both Systemic and Mucosal Immune Responses To Protect Ducks against Virulent DPV Infection

“…Local IgA was present to mediate protection in all organs sampled, which was consistent with previous studies showing that IgA is an effector molecule of the mucosal immune system (38)(39)(40). The production and distribution of local IgA in various organs in the present study are consistent with DPV having extensive tropism in all organs and local cells which can be stimulated to secrete IgA (19,41).…”

A Neonatal Fc Receptor-Targeted Mucosal Vaccine Strategy Effectively Induces HIV-1 Antigen-Specific Immunity to Genital Infection

“…Of note is the observation that Gag-binding IgG levels in BAL fluid or vaginal wash fluids were much higher than the specific IgA levels detected. Indeed, IgG is a major isotype of immunoglobulin in the lower respiratory and reproductive tracts (31,39). Thus, IgG antibodies detected in BAL and vaginal wash fluids may be produced locally or come from the circulation, but it was clear that HIV antigen targeted to FcRn plus adjuvant produced strong humoral and T cell mucosal immune responses.…”

“…In our study, FcRn-targeted mucosal vaccination induced significant amounts of Gag-specific IgG in serum, BAL fluid, and vaginal secretions. IgG is a major protective antibody in vaginal secretions after immunization (26,31,39). The potential roles for antibody produced by FcRn-targeted HIV gp120 antigen immunization may be more important for full protection in humans.…”

Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus

“…These polymeric IgA forms are associated with the extracellular portion of the polymeric Ig receptor, generating a complex (receptor + polymeric IgA) called S-IgA (9). S-IgA primarily corresponds to dimeric IgA, although low levels of some larger polymeric forms, particularly tetramers, are also present (9)(10)(11)(12)(13)(14)(15). Polymeric S-IgA has been shown (both in vitro and in experimental animal models) to be more effective than monomeric IgA or IgG for the neutralization of influenza viruses (16)(17)(18)(19).…”