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63 Mucosal Delivery of Canarypox Expressing Human Immunodeficiency Virus or Rabies G Proteins
P. Wright*, J. Mestecky, J. McElrath, M. Keefer, G. Gorse, P. Goepfert, D. Schwartz, P. Spearman, R. El Habib, J. Flores, and K. Weinhold
NIAID HIV Vaccine Trials Network
Background: As the primary routes of HIV acquisition are across mucosal barriers, a phase I randomized, clinical trial of canarypox-based vectors (ALVAC) was conducted in 84 human volunteers with delivery of vaccines by mucosal routes. A detailed analysis of cellular, mucosal, and humoral responses has been carried out.
Methods: HIV (vCP 205-10 6.7) and rabies (vCP 65-10 6.3) canarypox vectors were delivered systemically or into the nose, mouth, vagina, or rectum in a 4-dose schedule over 6 months followed by 2 doses of MN rgp 120 I.M. Samples were taken from all mucosal sites to detect antibody responses to HIV, rabies, and canarypox. Systemic HIV-specific CTL responses were determined by chromium release.
Results: Vaccine administration and sample collection were well tolerated. Canarypox was not recovered from mucosa at 4(8 or 24 hours. The only serious adverse reactions were 1 malaise after oral and 1 local erythema after I.M. vaccine. Serum IgG rabies antibodies were detected in 5/5 volunteers receiving vCP65 systemically whereas 0/6 had an antibody rise with mucosal administration. Serum HIV antibodies to gp120 were seen in 0/9 receiving systemic and 0/14 receiving mucosal vaccine. Serum canarypox IgG antibodies were seen in 6/6 after systemic but 0/14 mucosal vaccinations. Consistent mucosal responses at saliva, nasal, vaginal, and rectal sites to HIV, rabies, and canarypox were not seen. Hints of a mucosal response were systemic CTLs in 3/7 rectal, 1/7 nasal, and 1/7 oral vaccinees.
Conclusions: Each of the explored routes of vaccine administration was feasible in the context of a phase I study with motivated volunteers. Gp120 is less immunogenic than rabies. Judging by the lack of serum antibody responses, canarypox vectors did not effectively express inserted proteins at mucosal sites. Although canarypox in the dose and routes given was not an effective mucosal immunogen, this study provides a template for future evaluation of vaccines given by mucosal routes. Other vaccines, after preliminary data in animal models or a theoretical basis for presuming mucosal effectiveness, need to be evaluated in protocols such as this.
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