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

ted, our vaccination protocols have been changed to
Include chiupanzees. However we feel that further
characterising the African Green monkey as an alternative model is important since the chimpanzee model has
several limitations. Chimpanz2es are difficult to
obtain in la:ge enough numbers to cenduct a vaccination
protocol. They are expensive to maintain. Although
chimpanzees can be chronically infected with HIV, they
remain clinically well (10). African green monkeys may
prove to be a useful model since enough animals to
conduct a vac-in tion trial can be obtained and maintained at a relatively low cost. Preliinary experiments
with Africian green monkeys established that this
species can be infected with HIV. Future experimentation
revealed that using the original protocol, not all
monkeys responded with full evidence of infection and
an anti-HIV immune response. Full evidence of infection
was defined as reverse transcriptase (RT) activity in
supernatants of peripheral blood lymphocytes (PBL),
immunofluorescent staining of PHA activated PBL, HIV
transmission to T cells and an intergrated HIV genomic
pattern southern blot DNA hybridization. Experiments
to determine the protocol necessary to inaect 100% of
African green monkeys were begun. Parameters studied
included:
a) Varying the strain of African green monkey.
Three strains, Cercoithecus aethiops, C.
ascarius and C. cerebs wore teated;
b) Varying the HIV strain, HIV 1 and HIV 2
were tested;
c) Varying the route of infection. Intravenous (IV) and intraperitoneal (IP) routes
were investigated;
d) Varying the number and dose of virus.
We have not conducted any studies with RTLV-IIIX1O-I mutant virus since vaccination with live mutant
HIV 'virus is not practical due to possibility of reversion to virulence. Therefore, the immune response to
recombinant vaccinia-RHIV virus containing gene sequences to HIV gpl60 has been studied. Because T cells can
play an important role in host defense againsL viral
infectious t13), it is important to investigate T cell
mediated immunity in "raccin&ted or infected monkeys.
Both T cell mediated lysis of infected targets and
antigen induced cellular proliferation have been investigated. Serological studies have also been conducted.
Investigations into cytopathogenie mechanisms of
MIV infection have been conducted by comparing results

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