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Recombinant influenza viruses hold promise as vectors for vaccines to prevent transmission of mucosal pathogens. In this study, we generated a recombinant WSN/TatΔ 51-59 virus in which Tat protein lacking residues 51 to 59 of the basic domain was inserted into the N-terminus of the hemagglutinin (HA) of A/WSN/33 virus. The TatΔ 51-59 insertion into the viral HA caused a 2-log reduction in viral titers in cell culture, compared with the parental A/WSN/33 virus, and severely affected virus replication in vivo. Nevertheless, Tat-specific antibodies and T cell responses were elicited upon a single intranasal immunization of BALB/c mice with WSN/TatΔ 51-59 virus. Moreover, Tat-specific immune responses were also detected following vaccine administration via the vaginal route. These data provide further evidence that moderately large HIV antigens can be delivered by chimeric HA constructs and elicit specific immune responses, thus increasing the options for the potential use of recombinant influenza viruses, and their derivatives, for prophylactic and therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Mauritian cynomolgus macaques (MCM) are widely used in human immunodeficiency virus research because of their restricted major histocompatibility complex (MHC) diversity which provides the opportunity to address the influence of host factors on vaccine studies. We herein report the impact of MHC haplotype on the outcome of 21 MCM infections with the CCR5-tropic simian/human immunodeficiency virus (SHIV)SF162P4cy. MCM were susceptible to SHIVSF162P4cy infection as shown by viremia and loss of CD4+ T cells. A significant association between haplotype M7 (class I A, I B, II) and persistent viremia was observed in chronic phase, whereas recombinant class I A haplotype was associated with a reduction of viral RNA during acute infection. Class I B M4 haplotype displayed significantly lower acute phase provirus copy numbers. In addition, statistical analysis indicated a detrimental effect of haplotype M4 (class I A, I B) on the course of infection as indicated by lower CD4+ T-cell levels during chronic infection. A decrease in post-acute phase CD4+ T-cell numbers was also observed in haplotype M2 animals. This is the first report that documents the effects of host MHC class I and II molecules on the SHIVSF162P4cyinfection in MCM, particularly with regard to the association between recombinant class I A, M4, and M7 haplotypes and the dynamic of viral replication and level of CD4+ T cells. [ABSTRACT FROM AUTHOR]

Cynomolgus macaques are frequently used in biomedical research. However, in contrast to their closest relative, the rhesus macaque, little is known about their Mhc genes except for the DQB1 locus. In this study, 33 DRB-sequences belonging to 17 allelic lineages were detected in a total of 68 macaques, 58 originating from Mauritius and 10 from China. The majority of the sequences were detected in the few macaques from China, confirming the low degree of genetic variation in macaques from Mauritius. In summary, the DRB region in cynomolgus macaques is polymorphic. The sequences belong in general to the same allelic lineages as in their closest relative, the rhesus macaque. Two exon 2 DNA sequences were identical in both species and may represent a trans-species origin. In addition, protein sequences of members of the DRB*W1 lineage seem to be rather conserved in the three macaque species examined so far. Six DRB-haplotypes were detected in the macaques from Mauritius. While single DRB-alleles or some protein sequences seemed to be conserved among macaque species, we could not detect any evidence for a trans-species conservation of a complete DRB region. Overall, the data indicate that reorganization of the DRB region by recombination is a major force in creating diversity in cynomolgus macaques as it is in rhesus macaques. [ABSTRACT FROM AUTHOR]

Investigates the potential therapeutic utility of thalidomide (Thd), an effective inhibitor of tumor necrosis factor (TNF)-alpha in vitro, in cynomolgus monkeys at ten months after infection with simian immunodeficiency virus (SIV). Restoration by Thd of the proliferative responses to SIV peptides in monkeys infected with SIV; Non-observation of a reduction in either cell-associated viral load or plasma viral RNA among the SIV-infected monkeys during the two treatment cycles, when compared with the placebo group.

Mauritian cynomolgus macaques (MCM) are widely used in human immunodeficiency virus research because of their restricted major histocompatibility complex (MHC) diversity which provides the opportunity to address the influence of host factors on vaccine studies. We herein report the impact of MHC haplotype on the outcome of 21 MCM infections with the CCR5-tropic simian/human immunodeficiency virus (SHIV)SF162P4cy. MCM were susceptible to SHIVSF162P4cy infection as shown by viremia and loss of CD4+ T cells. A significant association between haplotype M7 (class I A, I B, II) and persistent viremia was observed in chronic phase, whereas recombinant class I A haplotype was associated with a reduction of viral RNA during acute infection. Class I B M4 haplotype displayed significantly lower acute phase provirus copy numbers. In addition, statistical analysis indicated a detrimental effect of haplotype M4 (class I A, I B) on the course of infection as indicated by lower CD4+ T-cell levels during chronic infection. A decrease in post-acute phase CD4+ T-cell numbers was also observed in haplotype M2 animals. This is the first report that documents the effects of host MHC class I and II molecules on the SHIVSF162P4cyinfection in MCM, particularly with regard to the association between recombinant class I A, M4, and M7 haplotypes and the dynamic of viral replication and level of CD4+ T cells. [ABSTRACT FROM AUTHOR]