RESUMO
The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies.
RESUMO
A retrospective study spanning 20 years was undertaken to investigate the prevalence and modes of transmission of a simian T-cell lymphotropic virus (STLV) in a closed breeding colony of chimpanzees. Of the 197 animals tested, 22 had antibodies that were cross-reactive with human T-cell lymphotropic virus type-1 (HTLV-I) antigens. The specificity of the antibody response was confirmed by Western blot analysis and the presence of a persistent virus infection was established by PCR analysis of DNA from peripheral blood mononuclear cells. Sequence analysis revealed that the virus infecting these chimpanzees was not HTLV-I but STLV(cpz), a virus that naturally infects chimpanzees. The limited number of transmission events suggested that management practices of social housing of family units away from troops of mature males might have prevented the majority of cases of transmission. Evidence for transmission by blood-to-blood contact was documented clearly in at least one instance. In contrast, transmission from infected mother to child was not observed, suggesting that this is not a common route of transmission for STLV in this species, which is in contrast to HTLV-1 in humans.
