Priming with T helper cell epitope peptides enhances the antibody response to the envelope glycoprotein of HIV-1 in primates.

The induction of a memory immune response to HIV, mediated by any kind of effector mechanism, requires the induction of T cell help. In previous studies performed in different murine MHC haplotypes, three immunodominant T cell epitopes (T1, T2, and TH4.1) had been identified in the HIV envelope glycoprotein. Moreover, these peptides were proliferative T cell epitopes in humans. In this study, rhesus monkeys, Macaca mulatta, were primed with these three peptides either in combination or given separately. Half of the monkeys had a proliferative response to one or more of the priming peptide(s). Those monkeys who had a T cell proliferative response also had a high antibody response after one boost with a suboptimal dose of the native protein gp 160, whereas three of four control monkeys who had received only the native protein immunization gave no detectable antibody response, and one displayed a very weak response. For reasons that are unclear, antibodies only to the gp41 portion of gp 160 could be detected in the sera. Thus, the peptides can prime Th cells in primates for an enhanced antibody response on first exposure to the whole protein. The three peptides belong to highly conserved and nonglycosylated regions of the envelope protein. The fact that the peptides acted as immunogenic T cell proliferative and helper epitopes in nonhuman primates is very encouraging for including them in future vaccine studies in humans.

Effects of three methods of restraint an in rhesus and african green monkeys intravenous glucose tolerance testing.

The intravenous administration of 0.75 gm glucose per kg and the measurement of serum glucose pretest and at 10, 20, 30, 60, 90 and 120 minutes constitute a satisfactory protocol for intravenous glucose tolerance testing of Rhesus (Macaca mulatto) and African Green (Cercopithecus aethiops) monkeys. No significant differences were noted between animals restrained with ketamine hydrochloride and those restrained with sodium pentobarbital, but the African Green males and females and the male Rhesus monkeys yielded significantly different results while being manually restrained.

Serological investigation of an outbreak of simian varicella in Erythrocebus patas monkeys.

An epizootic of simian varicella occurring in a colony of Erythrocebus patas monkeys was studied serologically by using radioimmunoassay and neutralization tests against (i) a virus strain isolated from an animal that died during the epizootic, (ii) a simian varicella virus strain from an earlier outbreak of simian varicella-like disease at another facility, and (iii) human varicella-zoster virus. Serological tests detected more cases of infection among the animals exposed to virus during the epizootic than were evidenced by clinical findings; only 6 of the 26 animals with seroconversion developed a rash. Good correlation was seen between antibody responses demonstrated by radioimmunoassay and by the neutralization tests. Specificity of the radioimmunoassay was evidenced by the complete agreement with neutralization results for 17 animals which failed to show an antibody response over the course of the outbreak and were assumed not to have been infected. Thus radioimmunoassay is a reliable, rapid, and relatively economical method which could be used for serological screening of primates entering experimental colonies to identify those which might be potential sources of outbreaks through activation of latent simian varicella virus infection. Close correlation was seen between antibody responses to the virus strain from the current outbreak and the one from another epizootic, indicating that the two outbreaks were caused by antigenically similar viruses. Animals showing neutralizing antibody responses to the simian varicella viruses also showed responses to human varicella-zoster virus, which further substantiates the close antigenic relationship between human and simian varicella viruses.

Interferon prophylaxis against simian varicella in Erythrocebus patas monkeys.

Erythrocebus patas monkeys were given placebo or human leukocyte interferon (5 x 10(5) units/kg of body weight per day im) for five days during an epizootic of simian varicella. During the 14 days beginning with the first day of treatment, the attack rate for simian varicella was 14.3% (two of 14) among interferon recipients compared to 70% (nine of 13) among placebo recipients (P less than 0.025). Excluding animals with antibody to simian varicella when the study began, 18% (two) of 11 interferon recipients had symptoms of infection compared to 80% (nine) of 11 placebo recipients (P less than 0.025). The epizootic began in a room housing male animals. The incidence of infection in male placebo recipients was 100% (seven of seven) compared to 14% (one of seven) in male interferon recipients (P less than 0.01). The efficacy of interferon prophylaxis in the simian varicella model supports its continued evaluation for the management of human varicella in high-risk patients.

Electrocardiograms of nine species of nonhuman primates sedated with ketamine.

Electrocardiograms were studied in nine species of nonhuman primates sedated with ketamine hydrochloride. Electrocardiographic values were similar in all species although heart rate and other rate-related values (QT and PR intervals) were species-dependent. Arrhythmias were infrequent. Ketamine hydrochloride did not appear to induce marked alterations in the ECG of primates.