The acquired immunodeficiency syndrome (AIDS) is the late-stage clinical manifestation of long-term persistent infection with the human immunodeficiency virus type 1 (HIV-1). Immune responses directed against the virus and against virus-infected cells during the persistent infection fail to mediate resolution of the infection. As a result, a successful AIDS vaccine must elicit an immune state that will prevent the establishment of the persistent infection following introduction of the virus into the host. The third hypervariable (V3) domain of the HIV-1 gp120 envelope glycoprotein is a disulphide-linked closed loop of about 30 amino acids which binds and elicits anti-HIV-1 type-specific virus-neutralizing antibodies. The in vitro characteristics of anti-V3 domain antibody suggest that this antibody could by itself prevent HIV-1 infection in vivo, an idea supported by chimpanzee challenge studies in which protection against the HIV-1 persistent infection seemed to correlate with the presence of anti-V3 domain antibody. Here we directly demonstrate the protective efficacy of anti-V3 domain antibody in vivo and propose that this antibody is potentially useful as both a pre- and post-exposure prophylactic agent.

A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1MN gp160 recombinants followed by boosting with HIV-1SF2 gp120 was evaluated in chimpanzees. Long-lasting protection, requiring only three immunizations, was achieved against a low-dose challenge with the SF2 strain of HIV-1 and a subsequent high-dose SF2 challenge administered 1 year later without an intervening boost. Notably, neutralizing antibody responses against both clinical and laboratory isolates developed in three chimpanzees and persisted until the time of high-dose challenge. The possibility that cytotoxic T-lymphocytes contribute to low-dose protection of a chimpanzee lacking neutralizing antibodies is suggested. Our results validate the live vector priming/subunit booster approach and should stimulate interest in assessing this combination vaccine approach in humans.

The use of a human immunodeficiency virus (HIV) immune globulin (HIVIG) in prevention of HIV infection in chimpanzees was investigated in the hope of ultimate application to interruption of vertical transmission. In previous experiments, no protection was observed when relatively high challenge doses were used. This study shows that HIVIG protected against a challenge dose (10 CID50) tenfold lower than that used previously. The protected animal remained free of HIV infection as determined by cocultivation and by polymerase chain reaction (PCR), and did not mount a primary immune response detectable by enzyme-linked immunosorbant assay (ELISA) and neutralization assays. These results imply that HIV vaccines should induce neutralizing antibody and may not need to induce cell-mediated immunity in order to be protective against exposure to HIV. They also provide an experimental basis for the conduct of clinical trials to evaluate prevention of maternal-infant transmission by HIVIG.

A relationship between sex steroids and the somatomedins (Sms) is well known, but poorly defined. In some primates, including man, there are pubertal increases in Sms, concurrent with increased growth and sex steroid production. In the current studies, indices of somatic growth [body weight, crown-rump length (CRL), and testis size (testicular volume index)] and circulating concentrations of testosterone (T), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), cortisol, and Sm-C were determined (n = 208) in 86 male and female chimpanzees during a 1-yr period. In addition, we have attempted to determine whether plasma Sm-C concentrations correlate with serum levels of estrogen and androgens. In male animals between 6 and 8 yr of age, there was a marked increase in testicular size, concurrent with an increase in serum T and preceding slightly an increase in the rate of body weight gain. There were no detectable increases in serum E2 or the CRL slope. In females between 6 and 8 yr of age, serum T increased, concurrent with an increase in the rate of body weight gain much smaller than that in male animals. Serum E2 increased only after 10 yr of age, and no increased linear growth (CRL) was found. In both sexes, increases in serum DHEA-S were found by 4-6 yr of age, in contrast to cortisol concentrations, which were high and remained unchanged from birth to 12 yr of age, except for lower values in the very youngest and very oldest female animals. An increase in Sm-C occurred in both sexes by 4-6 yr of age, with higher values in female than in male animals 0-2, 4-6, and 6-8 yr of age, and when all ages were considered together. In both sexes, plasma Sm-C concentrations correlated with serum T (r = 0.60 and P less than 0.001; r = 0.68 and P less than 0.001; females and males, respectively), although when both sexes were analyzed together, the correlation was not as good (r = 0.36; P less than 0.001). Sm-C concentrations correlated with serum DHEA-S when the two sexes were analyzed separately (r = 0.44 and P less than 0.001; r = 0.54 and P less than 0.001; females and males, respectively) or together (r = 0.49; P less than 0.001). Sm-C correlated poorly with serum E2 levels in females (r = 0.20; P less than 0.05) and did not correlate with E2 in males.(ABSTRACT TRUNCATED AT 400 WORDS)