Intranasal Immunization Is Superior to Vaginal, Gastric, or Rectal Immunization for the Induction of Systemic and Mucosal Anti-HIV Antibody Responses

Abstract

Vaginal anti-HIV antibody responses may be beneficial, and possibly required, for vaccine-induced protection against HIV infection acquired through receptive vaginal intercourse. We have previously determined that intranasal immunization with a hybrid HIV peptide and cholera toxin induced vaginal anti-HIV IgA responses in BALB/c and C57BL/6 mice. To determine if vaginal, gastric, or rectal boosting would enhance the induction of vaginal anti-HIV IgA responses over those observed with intranasal immunization only, C57BL/6 mice were intranasally immunized with the hybrid HIV peptide T1SP10MN(A) and cholera toxin (days 0 and 14) and boosted via the vaginal, gastric, or rectal route (days 7 and 28). Four intranasal immunizations was superior to all other immunizations evaluated for the induction of plasma anti-peptide IgG, vaginal anti-peptide IgG and IgA, and peptide-specific delayed-type hypersensitivity. In addition, intranasal priming with gastric boosting was associated with greatly elevated total serum IgE concentrations whereas intranasal immunization only was associated with only a modest increase in total serum IgE. These results suggest that intranasal immunization is a viable route of immunization for the induction of systemic and mucosal anti-HIV immune responses.

A Novel Functional CTL Avidity/Activity Compartmentalization to the Site of Mucosal Immunization Contributes to Protection of Macaques against Simian/Human Immunodeficiency Viral Depletion of Mucosal CD4+ T Cells

“…Indeed, our previous studies (7,8) and studies of other groups (9,(33)(34)(35)(36) demonstrated a strong rationale for development of a mucosal AIDS vaccine to generate sufficient mucosal immune responses (both mucosal Ab and CD8 ϩ CTL) to keep the virus under control locally in the gut mucosa and in the systemic circulation as well. We showed that in mice, a mucosal vaccine can be more effective than the same vaccine given s.c. and this protective effect is mediated by mucosal CD8…”

Long-Term Control of Simian Immunodeficiency Virusmac251 Viremia to Undetectable Levels in Half of Infected Female Rhesus Macaques Nasally Vaccinated with Simian Immunodeficiency Virus DNA/Recombinant Modified Vaccinia Virus Ankara

“…The nasal route is particularly attractive because of its simplicity and proven efficacy (16)(17)(18). Significant mucosal and systemic responses might be achieved after nasal immunization in primates with an appropriate adjuvant and boosting regimen.…”

Differential Induction of Mucosal and Systemic Antibody Responses in Women After Nasal, Rectal, or Vaginal Immunization: Influence of the Menstrual Cycle

“…If N imm induces both rectal and genital tract mucosal immune responses, it could be a more effective mucosal administration route for STD vaccines, because R imm and V imm , though highly effective for induction of local responses, generate little or no specific IgA at distal mucosal sites (7-9, 29, 30). Studies in mice have also suggested that N imm might be economically advantageous to other mucosal immunization routes because lower Ag doses can generate mucosal Ab responses comparable to those induced by higher doses administered elsewhere (6,31,32). To determine whether this may be the case in humans, we administered 10-fold lower cholera vaccine doses in the nasal cavity of women and compared the magnitude of the mucosal and systemic Ab responses generated to those induced by higher doses in women who received V-FP imm , V-LP imm , or R imm .…”