HUMAN SAFETY AND IMMUNOGENICITY OF A CANARYPOX-RABIES GLYCOPROTEIN RECOMBINANT VACCINE - AN ALTERNATIVE POXVIRUS VECTOR SYSTEM

Avian poxvirus recombinants undergo abortive replication in nonavian c ells, yet can achieve expression of extrinsic gene products. Canarypox -vectored vaccines have been innocuous and immunogenic in several mamm alian species. ALVAC-RG, a canarypox recombinant expressing the rabies glycoprotein gene, was inoculated intramuscularly into adult voluntee rs on days 0, 28, and 180. Sequential cohorts received 10(3.5), 10(4.5 ) and 10(5.5) 50% tissue culture infective doses (TCID50); additional volunteers received the standard human diploid cell rabies vaccine (HD CV) on the same schedule. Reactogenicity of ALVAC-RG was minimal The l owest dose of ALVAC-RG induced little antibody to rabies virus by ELIS A or rapid fluorescent focus inhibition rest (RFFIT), but 10(4.5) and 10(5.5) TCID50 doses elicited significant responses in both assays. Al l recipients of 10(4.5) and 10(5.5) TCID50 of ALVAC-RG attained RFFIT values above the presumed protective level. Canarypox-specific immune responses did Mot inhibit boosting of rabies-specific antibodies by th e day 180 dose of ALVAC-RG. T cell proliferation in response to inacti vated rabies virus in vitro was similar in HDCV and ALVAC-RG recipient s after the first and second doses, although HDCV yielded superior res ults after the third dose. ALVAC-RG was safe in humans, induced functi onal antibody to rabies glycoprotein, elicited cellular responses to r abies virus, and could be used successfully for booster dosing at a 6 month interval. Copyright (C) 1995 Elsevier Science Ltd.