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The dichotomy of type-1 and type-2 T-helper (Th) immune responses is thought to be an obstacle to develop Human immunodeficiency virus-type- (HIV-1) vaccines capable of inducing effective cellular as well as humoral immune responses. Macaca mulatta were immunized using two different HIV-1sf2 envelope vaccine strategies, based on either immune-stimulating complexes (ISCOM) or chimeric Fowlpox (FP) vaccines. One month following the third immunization all animals were heterologously challenged with simian/human immunodeficiency virus (SHIVsf13). Vaccinated monkeys, which were protected had the highest levels of both type-1 and type-2 HIV-1 specific T-helper cell (Th) responses in addition to the highest homologous and heterogenous virus neutralizing antibodies. To determine how long Th responses persisted and if they correlated with protection, animals were rechallenged after waiting for four months without re-boosting. Macaques which maintained the highest gp120-specific type-1 (IFN-gamma) responses were protected, while there was evidence of viral clearance in two others. These findings demonstrate the importance of both or mixed type-1 and type-2 Th responses in HIV-1 vaccine induced immunity while suggesting a possible role of persistent type-1 responses in maintaining protective immunity over time.

SummaryWe evaluated the in vitro and in vieo antiviral activity of the deoxyribonucleoside analoDlJe 5.iodo·2'·deoxy-cytidine (IDC) combined with the dihydrofolate reduc-. tase inhibitor methotrexate (MTX) on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). The IDC-MTX combination synergistically inhibited HSV-1 and HSV-2 replication in vitro at concentrations that did not reduce cellular viability and was very effective in reducing the severity of cutaneous lesions in the experimental guinea pig model in vivo. The antiviral activity of the IDC-MTX combination in guinea pigs was also compared with that of acyclovir and was demonstrated to be higher.

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The fine immunoreactivity of the rabbit humoral response elicited by four env-recombinant avipoxviruses and their ability to stimulate a memory T-cell response and a protective immunity have been studied. The antibody specificity was compared with the serum neutralizing activity and virus-specific T-cell proliferative response. Resistance to challenge by cell-associated HIV-1 was monitored by PCR. Canarypox (CP) and fowlpox (FP) constructs, containing the complete env gene (IS(+)) from the HIV-1(SF2) strain, induced a higher profile of epitope recognition than their counterparts expressing the env gene deleted of the putative immunosuppressive region (IS(-)). Serum neutralizing activity was in agreement with fusion inhibition and lymphoproliferative response in rabbits immunized with CPIS(+), and only partially with FPIS(+). Rabbits failed to be infected, but anti- p55 gag-specific antibodies could be demonstrated by Western blot. This study confirms the ability of these non-replicative live recombinant viruses to elicit a complete immune response, capable of inhibiting specific HIV-1 functions.