Development and Evaluation of Adeno-HTLV-III Hybrid Virus and Non-Cytopathic HTLV-III Mutant for Vaccine Use

Bivalent immunization with live, attenuated Ad
type 4 'nd type 7 has proven~ to be both safe and effective in military recruits over a period of 20 years
(24,25,26). This vaccine, which is administered orally
in enteric-coated capsules, liberate; virus into the
intestine where a subclinical infection is established
that confers a high degree of immunity. Successful
imaunization with Ad types 1, 2 and 5 by this route
have also been demonstrated (27). The fact that administration of live vaccinis by the gastrointestinal
route may facilitate spread of the Ad (28) may be advantageous in immunizing against HIV if a suitatle, relatively non-pathogenic strain of adenovirus is;sed as
vector. The majority of Ad infections result in selflimiting and short-lived clinical manifestations althotvlh
prolonged asymptomatic or latent infections may occur
(29). It is possible that reactivation of latent adcovirus, as has been proposed to occasionally occur in
rubella infectiops (G0), may provide a mechanism for a
natural lIV "booster" immunization in the case of the
rAd vaccine.
Ad structural proteins are synthesized in large
quantities during infection and at least 8t of vi',al
hexon, penton and fiber are not incorporated into
progeny virus but remain in the infected cell in the
form of readily soluble multimers (31). Theoretically,
exogenous DNA sequences stably integrated into the Ad
genome under the control of the major late promoter
might also be expressed at a high level to provide a
source of immunogen.
Ad is very stable and can toletate temperatures of
4-36'C and pH 5-9 with minimal loss of infectivity,
thus, alleviating many problems associated vich vaccine
transport and storage especially in under-developed
countries.
The technology necessary to propagate large quantities of Ad to produce an enteric-coated vaccine is presently available so that production of a rAd vaccine
should not require the development of new manufacturing
processes.
This project is designed to investigate the fesmbility of using infectious Ad to produce gvl20 or other
STY immunogen and to determine whether these IV antigens would be presented in such a way as to tlicit
protective irsunity in the host.
C. Rationale
Since chimpanzees are the only non-human primste
whose ability to be infected with IV is well documen