Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

636 Abstracts 33219-33222

12th World AIDS Conference

env gene, 83 of which were also analysed by restriction fragment length polymorphism (RFLP) in the gag p17 region. Partial env subtype C sequences from
eight South African samples were phylogenetically analysed with all published
Southern African subtype C sequences as well as representative sequences from
other global subtype C epidemics to identify a representative Southern African
strain. A gp120 fragment from each prevalent South African subtype was inserted
into the pcDNA3.1 DNA vaccine vector. Transient expression of the gp120 DNA
vaccine was performed in HeLa cells and mice were i.m. immunised with 100 itg
of DNA, then given three boosts to determine the antibody response to the DNA
vaccine.
Results: It was found that 164 out of 177 heterosexual samples from South
Africa were subtype C and 35 out of 39 homosexual samples from Johannesburg
and Cape Town were subtype B. Five subtype A's and two subtype D's were
also identified. The gp120 of subtypes A, B and C was inserted into pcDNA3.1
and transiently expressed in HeLa cells detected by immunofluorescence. When
injected into mice a low titre antibody response was detected.
Conclusion: Subtype C is the predominant subtype in the heterosexual population of South Africa. The association between subtype B and homosexual
transmission in samples from Johannesburg confirms the results of a previous
study performed in Cape Town. South African subtype C's are highly divergent
and no major subclusters were identified in the env sequences analysed from
South Africa. The gp120 was expressed and CTL response and cross-reaction
by the different DNA vaccines need to be analysed.
33219 Recruitment of volunteers into a randomized, placebo
controlled phase I HIV-1 vaccine trial in Uganda
Anthony Kebba1, C. Othiendo1, K. George2, D. Hom2, P. Mugyenyi1,
R. Mugerwa3, J. Ellner2. 1Joint Clinical Research Centre, PO Box 10005,
Kampala; 3Makerere University, Kampala, Uganda; 2Case Western Reserve
University Cleveland, OH, USA
Objectives: 1) Recruitment of 40 HIV-1 uninfected healthy adult Ugandan volunteers at low risk for HIV seroconversion to a phase I HIV-1 vaccine trial; and 2)
establish EBV transformed B-Lymphoblastoid cell lines (B-LCL) from these adult
Ugandans volunteers for use as target cells in the later trial.
Methods: Proposed is a double-blinded, 3-arm placebo-controlled phase I trial
of the safety/immunogenicity of a recombinant HIV-1 canarypox vector vaccine
(ALVAC vCP205- Pasteur-Merieux Connaught). Twenty HIV seronegative volunteers will receive 4 doses of ALVAC vCP205 over a 6-month period and 10
volunteers each will receive a similar schedule of ALVAC-RG (rabies vaccine)
or a placebo (saline). Required are healthy HIV uninfected adults (18-40 yrs); at
low risk for HIV; understand the trial and provide informed consent; with no medical conditions that will interfere with conduct; and who have established viable
EBV (Epstein-Barr virus) transformed B cell lines. Volunteers are recruited from
ongoing cohorts with blood drawn for establishment of EBV transformed B-LCL.
Primary endpoints are cytotoxic T-Lymphocyte responses, neutralizing and binding antibodies, and safety. Successful transformation of B-LCL is confirmed by
continued presence of proliferation.
Results: 158 people were approached and 93 (76 males & 17 females) were
eligible for screening. The majority have been followed for 1 year as the trial
awaits final government approval, with losses minimal: pregnancy (5); multiple
sex partners (3); poultry worker (1); and withdrawn consent (1). All initially indicated willingness to participate and understood the informed consent process.
A 90% success rate has been observed with the EBV B-LCL transformations,
assuring that everyone eligible for the trial could eventually participate given a
successful target cell line.
Conclusion: Though there was a high degree of initial motivation to participate
in HIV vaccine trials, the enthusiasm waned awaiting approvals. Continued education/counseling from screening to throughout the trial will be critical in ensuring
compliance and avoiding withdrawal. The induction of HIV specific CTLs is an
important measurement of candidate vaccines. Our reported success rate for
EBV B-LCL transformation are encouraging and support on going efforts in the
study of CTL responses as pertaining to vaccine strategies.
33220 Clinical response to HIV Thai E/MF59 vaccine administer
of alone or combined with SF2 gp120 antigen in healthy
volunteers
Punnee Pitisuttithum1, C. Khamboonruang2, P. Suntharasamai1,
S. Thongsawat2, S. Migasena1, Y. Yutabutr2, B. Phonrat1. ' Vaccine Trial Centre
Faculty of Tropmed 42016 Rajvithi Road Rajtheve Bangkok 10400; 2Rihes
Chiang Mai University Chiang Mai, Thailand
Objective: To determine the safety of three doses of HIV Thai E gp120/MF59
vaccine alone or combined with SF2 gp 120 antigen in healthy HIV-1 seronegative
Thai adults.
Design: Open - labeled, dose escalating study.
Method: Groups of three healthy HIV seronegative volunteers were sequentially blocked enrolled to one of 4 antigen/dose combination: 25 ug of Thai E

gp120/MF59 (Group 1), 25 ug of Thai E gp120/MF59+25 ug SF2 gp 120/MF59
(Group II), 100 ug of Thai E gp120/MF59 (Group III) and 100 ug of Thai E
gp120/MF59+50 ug SF2 gp120/MF59 (Group IV). Sequential enrollment to each
group was separated by 48 hrs and required that the preceding group to be free
of serious reactogenic reactions. Immunizations were given at 0, 1, 6 months. All
volunteers were evaluated 24-48 hours after vaccination and were required to

record daily symptoms for 6 days post immunization. Up to the time of submission
to abstract, only two doses of vaccination have been administered.
Results: Reported local and systemic symptoms by vaccine dose and number
of vaccinations
Group I Group II Group III Group IV
1st Vac 2nd Vac 1st Vac 2nd Vac 1st Vac 2nd Vac 1st Vac 2nd Vac
Pain at injection site 2/3 1/3 3/3 3/3 3/3 3/3 3/3 3/3
Warmth to injection site 1/3 0/3 0/3 0/3 2/3 0/3 1/3 1/3
Malaise 0/3 0/3 1/3 2/3 0/3 1/3 1/3 0/3
Fever (> 38 C) 0/3 0/3 0/3 1/3 0/3 0/3 0/3 0/3
Conclusion: Thai E gpl20/MF59 vaccine administered alone or combined with
SF2 gp 120 antigen appears to be safe. No serious adverse events have been
observed following two immunization
33221 CTL and neutralizing antibody responses with a
combination HIV-1 vaccine regimen
Lawrence Corey', K. Weinhold2, D. Montefiori2, D. Stablein3. 1University Of
Washington, Seattle WA; 2Duke University, Durham NC; 3Emmes Corporation,
Potomac MD, USA
Background: Protection from HIV is felt to require both cellular and humoral
immune responses.
Methods: Among seronegative volunteers, we compared the CD8+ CTL,
ADCC, neutralizing (Nt), and binding antibody (Ab) responses to a recombinant
canarypox vector (vCP205) consisting of gpl20MN, gag and pol given alone (n =
33); a gp120 subunit protein vaccine given alone (n = 24), or a combination regimen of both vaccines (n = 152) with appropriate placebo (n = 46). The vaccines
were administered singly, in combination, sequentially or simultaneously at 0, 1,
3, 6, 9, 12 or 0, 1, 6, 9, 12 month intervals.
Results: After 4 doses, vCP205 elicited CD8+ CTL responses to HIV-1 in 68%
and low titer Nt Ab (GMT 14) in 71% of recipients; gp120 alone produced (after
3 doses) Nt Ab in 100% (GMT 155) and no CD8+ CTL. The combination vaccine
regimens resulted in CTL responses in 56%, Nt Ab 92% (GMT 131), as well as
enhanced ADCC Ab and lymphoproliferative responses to HIV-1. CTL responses
to HIV-1 appeared after dose 2 of vCP205; 1/3 of persons responded to HIV env;
1/3 HIV gag and 1/3 to both env and gag. CTL responses were similar in those
with and without prior vaccinia immunization and among those who did and did
not receive gp120. Limiting dilution analyses revealed a pCTL frequency of 25
HIV-1 specific memory T cells/million PBMC, about 5 fold less than HIV infected
persons.
Conclusions: This combination vaccine regimen produces both humoral and
CTL responses to HIV. The precursor frequencies of CTL responses, lymphoproliferative responses, and the levels of ADCC, Nt and V3 binding Ab approach,
those required for protection or amelioration of infection. Studies to evaluate the
effectiveness of combination vaccines for preventing HIV-1 infection should be
considered.
S33222 Future planning for HIV vaccine evaluation of Thai AIDS
Vaccine Evaluation Group (TAVEG) in Thailand
Prasert Thongcharden1, S. Migasena1, C. Khamboonruang2, S. Nitayaphan3,
A. Brown2, C. Wasi1. 12 Prannok Rd, Dept Microbiology Fac. Med, Siraraj
Hospital Mahidol Univ., Bangkok; 2RIHES, Chiang Mai; 3AFRIMS, Bangkok,
Thailand
After WHO announced in 1991 that four member states (Brazil, Rwanda, Thailand
and Uganda) would be supported as HIV-1 vaccine testing sites, Thailand had
agreed to participate in this very important scientific study, which based the ground
that infrastructures for vaccine development have been well prepared. Since 1992
investigators in Thailand have conducted phase I or phase 1/11 evaluation of HIV
candidate vaccines: 1) Synvac HIV-1 octameric V3 peptide vaccine, 2) Phase
1/11 of MN rgp 120/HIV-1 alum adjuvant candidate vaccine, 3) Phase I trial of
Biocine HIV-1 SF2 rgp 120/MF59 vaccine, 4) Phase 1/11 of envelope-depleted
killed vaccine in infected individual, and, 5) Phase I/Il of Thai E rgp 120 alone or
combined with SF2 rgp 120 candidate vaccine.
Subcommittee on HIV Vaccine Development for Prevention and Therapy has
now given the revised guideline for HIV vaccine evaluation in Thailand which will
allow investigators to submit the evaluation proposal for Phase III evaluation. Thai
AIDS Vaccine Evaluation Group or TAVEG has been formed at 4 testing sites
(2 sites at Mahidol University - Faculty of Tropical Medicine, Faculty of Medicine
Siriraj Hospital, one site at the Research Institute for Health Science of Chiang
Mai Univeristy and one site at the Armed Forces Research Institute of Medical
Science). The group has planned to evaluate Phase I/Il Prime/Boost protocol
(Alvac:E + gp 120 or 160) and DNA vaccine in the very near future.
Conclusion: Results from several vaccine evaluation projects suggest that
candidate vaccines are save and immunogenic. TAVEG then plans to evaluate
more newer vaccines in phase 1/11 and phase III, if possible, in the near future.