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The precise immunological role played by [CD4.sup.+] T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental [CD8.sup.+] cell depletion, elite controlling macaques with set-point viral loads [less than or equal to] 500 viral RNA copies/mL mounted robust Gag-and Nef-specific [CD4.sup.+] T cell responses during reestablishment of control with [greater than or equal to] 54% of all virus-specific [CD4.sup.+] T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific [CD4.sup.+] T cells neither recognized nor suppressed viral replication in SIV-infected [CD4.sup.+] T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific [CD4.sup.+] T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific [CD4.sup.+] T cells may contribute directly to elite control by inhibiting viral replication in macrophages. antigen processing and presentation | HIV

The highly polymorphic gene products of the classical MHC class I genes in humans (HLA-A, HLA-B, and HLA-C) play a critical role in the immune defense against intracellular infections. Because nonhuman primates are important models for AIDS vaccine research, rhesus monkeys from a thoroughly pedigreed and serotyped colony were subjected to full-length cDNA analysis of MHC class I gene transcripts. Rhesus macaques express multiple dominant Mamu-A and Mamu-B transcripts (majors) per chromosome, which are characterized by high expression levels. The presence of additional cDNAs with low levels of expression (minors) suggests evidence for transcriptional control of MHC class I genes. Moreover, phylogenetic analyses illustrate that most of the Mamu-A and Mamu-B loci/lineages identified display no or only limited levels of allelic polymorphism. Thus, MHC class I diversity in rhesus macaques is typified by the existence of an unmatched high number of Mamu-A and Mamu-B region configurations that exhibit polymorphism with regard to the number and combination of transcribed loci present per chromosome. AIDS | non-human primate

A comparison between the HLA-B homologues of chimpanzee, humans and bonobos revealed recombination to characterize HLA-B loci, which is associated with the major histocompatibility complex (MHC). Human and chimpanzee HLA-B homologues, which exhibited similar alleles in exon 2, demonstrated different alleles in exon 3. MHC class I loci were molecules that enhanced peptide bond formation.

A comprehensive understanding of the development and evolution of human B cell responses induced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a highthroughput single B cell cloning technology to longitudinally track the human B cell response to the yellow fever virus 17D (YFV-17D) vaccine. The earlymemory B cell (MBC) response wasmediated by both classical immunoglobulin M (IgM) (IgM+CD27+) and switched immunoglobulin (swIg+) MBC populations; however, classical IgM MBCs waned rapidly, whereas swIg+ and atypical IgM+ and IgD+ MBCs were stable over time. Affinity maturation continued for 6 to 9mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination. [ABSTRACT FROM AUTHOR]

The biological characteristics of HIV pose serious difficulties for the success of a preventive vaccine. Molecularly cloned SIVmac239 is difficult for antibodies to neutralize, and a variety of vaccine approaches have had great difficulty achieving protective immunity against it in rhesus monkey models. Here we report significant protection against i.v. acquisition of SIVmac239 using a long-lasting approach to vaccination. The vaccine regimen includes a replicationcompetent herpesvirus engineered to contain a near-full-length SIV genome that expresses all nine SIV gene products, assembles noninfectious SIV virion particles, and is capable of eliciting long-lasting effector-memory cellular immune responses to all nine SIV gene products. Vaccinated monkeys were significantly protected against acquisition of SIVmac239 following repeated marginal dose i.v. challenges over a 4-month period. Further work is needed to define the critical components necessary for eliciting this protective immunity, evaluate the breadth of the protection against a variety of strains, and explore how this approach may be extended to human use. [ABSTRACT FROM AUTHOR]

Most animal studies using passive administration of HIV broadly neutralizing monoclonal antibodies (bnMAbs) have associated protection against high-dose mucosal viral challenge with relatively high serum concentrations of antibody. We recently identified several bnMAbs remarkable for their in vitro potency against HIV. Of these bnMAbs, PGT121 is one of the most broad and potent antibodies isolated to date and shows 10to 100-fold higher neutralizing activity than previously characterized bnMAbs. To evaluate the protective potency of PGT121 in viva, we performed a protection study in rhesus macaques. Animals were i.v. administered 5 mg/kg, 1 mg/kg, or 0.2 mg/kg PGT121 24 h before being vaginally challenged with a single high dose of chimeric simianhuman immunodeficiency virus (SHIV)SF162P3. Sterilizing immunity was achieved in all animals administered 5 mg/kg and 1 mg/kg and three of five animals administered 0.2 mg/kg PGT121, with corresponding average antibody serum concentrations of 95 μg/mL, 15 μg/mL, and 1.8 μg/mL, respectively. The results suggest that a protective serum concentration for PGT121 is in the single-digit μg/mL for SHIVSF162P3, showing that PGT121 can mediate sterilizing immunity at serum concentrations that are significantly lower than those observed in previous studies and that may be achievable through vaccination with the development of a suitable immunogen. [ABSTRACT FROM AUTHOR]

The precise immunological role played by CD4+ T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental CD8+ cell depletion, elite controlling macaques with set-point viral loads ≤500 viral RNA copies/mL mounted robust Gag-and Nef-specific CD4+ T cell responses during reestablishment of control with ≥54% of all virus-specific CD4+ T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific CD4+ T cells neither recognized nor suppressed viral replication in SIV-infected CD4+ T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific CD4+ T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific CD4+ T cells may contribute directly to elite control by inhibiting viral replication in macrophages. [ABSTRACT FROM AUTHOR]

Describes the presence of a major histocompatibility complex (MHC) class I processed pseudogene in the genome of several species of the genus Saguinus. Hallmarks of the MHC; Evolutionary stability of the loci; Materials and methods of the study; Details of the study.