Safety and Immunogenicity of a Canarypox‐Vectored Human Immunodeficiency Virus Type 1 Vaccine with or without gp120: A Phase 2 Study in Higher‐ and Lower‐Risk Volunteers

Abstract

Live attenuated viral vectors that express human immunodeficiency virus (HIV) antigens are being developed as potential vaccines to prevent HIV infection. The first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55, and protease) was conducted in 435 volunteers with and without gp120 boosting, to expand the safety database and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection. Neutralizing antibodies to the MN strain were stimulated in 94% of volunteers given vCP205 plus gp120 and in 56% of volunteers given vCP205 alone. CD8(+) cytotoxic T lymphocyte cells developed at some time point in 33% of volunteers given vCP205, with or without gp120. Phase 3 field trials with these or similar vaccines are needed, to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study.

Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients

“…28,29 The safety of the ALVAC canarypox virus as a vector as well as its ability to induce an immune response against the product of the incorporated gene has been well established in various malignancies 30,31 and infectious diseases. 15,[32][33][34] Other viral vectors may be less efficient owing to preexisting anti-viral antibodies, 35 the immunogenicity of the viral vector or toxicity. 36,37 For instance, a study in which adenovirus encoding wild-type p53 was injected intratumorally in patients with advanced non-small cell lung cancer did not result in the induction of an anti-p53 response.…”

HIV-1 Vaccination Administered Intramuscularly Can Induce Both Systemic and Mucosal T Cell Immunity in HIV-1-Uninfected Individuals

“…Healthy, HIV-1-uninfected adult volunteers reporting activities consistent with lower or higher risk of acquiring HIV-1 infection were eligible to participate in the study, and detailed enrollment criteria have been published (24). Vaccine recipients were injected i.m.…”

“…Each 0.5-ml dose contained 10 6 50% tissue culture-infective dose of virus. The rgp120 vaccine (Chiron, Emeryville, CA) was given as 0.5-ml doses containing 50 g of Ag in combination with MF59 adjuvant emulsion (24).…”

“…Canarypox vectors containing HIV-1 gene inserts have undergone extensive testing in phase I-II trials. Notably, live recombinant canarypox ALVAC-HIV vaccine (vCP205), 3 containing HIV-1 genes encoding env, gag, and portions of pol, has induced cumulatively HIV-specific CD8 ϩ CTL in the peripheral blood of 30 -50% of HIV-seronegative vaccine recipients (22)(23)(24). However, vaccine-induced mucosal CTL responses have not been assessed in these studies, and heretofore it has been unclear whether examination of sufficient numbers of mucosal T cells was feasible without subjecting volunteers to more invasive procedures to obtain the relevant mucosal samples.…”

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

“…Candidate vaccine vectors in more advanced stages of development are under evaluation in human clinical trials. Canarypox vectors are well tolerated, but their immunogenicity has been disappointing: HIV-specific CD8+ CTL responses measured at any one timepoint after vaccination are present in only 20-30% of human subjects [59,60]. While these phase I/II trials were not designed to test vaccine efficacy, breakthrough HIV infections have occurred with equal frequency in the vaccinated and unvaccinated control subjects [61].…”