Immunization of Newborn Rhesus Macaques with Simian Immunodeficiency Virus (SIV) Vaccines Prolongs Survival after Oral Challenge with Virulent SIVmac251

Abstract

There is an urgent need for active immunization strategies that, if administered shortly after birth, could protect infants in developing countries from acquiring human immunodeficiency virus (HIV) infection through breast-feeding. Better knowledge of the immunogenic properties of vaccine candidates in infants and of the effect of maternal antibodies on vaccine efficacy will aid in the development of such a neonatal HIV vaccine. Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model of pediatric HIVinfection with which to address these questions. Groups of infant macaques were immunized at birth and 3 weeks of age with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol, and Env (MVASIVgpe) or live-attenuated SIVmac1A11. One MVA-SIVgpe-immunized group had maternally derived anti-SIV antibodies prior to immunization. Animals were challenged orally at 4 weeks of age with a genetically heterogeneous stock of virulent SIVmac251. Although all animals became infected, the immunized animals mounted better antiviral antibody responses, controlled virus levels more effectively, and had a longer diseasefree survival than the unvaccinated infected monkeys. Maternal antibodies did not significantly reduce the efficacy of the MVA-SIVgpe vaccine. In conclusion, although the tested vaccines delayed the onset of AIDS, further studies are warranted to determine whether a vaccine that elicits stronger early immune responses at the time of virus exposure may be able to prevent viral infection or AIDS in infants.

Evaluation of Passively Transferred, Nonneutralizing Antibody-Dependent Cellular Cytotoxicity-Mediating IgG in Protection of Neonatal Rhesus Macaques against Oral SIVmac251 Challenge

“…In this regard, CD4 T cell counts declined somewhat by wk 2 postchallenge but not to exceedingly low levels (Fig. 1, C and D), which is consistent with previous studies on SIV mac251 -infected infant macaques (21,31). No difference in CD4 count was observed between neonates that received immune IgG or control IgG.…”

“…ϩ T cell counts compared with adults (21,30,31). Thus, this phenotype partly explains the high viral burdens because more target cells are available for viral infection.…”

“…The macaques were also monitored for weight, general health, and clinical signs and symptoms of disease progression. Animals were euthanized when necessary according to previously defined criteria (21).…”

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

“…Animal studies have demonstrated that neutralizing antibodies elicited by a simian immunodeficiency virus (SIV) vaccine can at least slow disease progression (56), while direct administration of antibodies matched to the chal-lenge virus can block transmission (16,44). Studies of natural MCTC have yielded conflicting results (2,3,7,20,26,31,32,48), although possibly for identifiable reasons.…”

Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine for rabies

“…eczematous, elderly or young), no untoward effects were reported and these reports have since been substantiated in clinical trials with MVA recombinants (e.g. [27], [28], [29] and [30]). This highly attenuated strain of vaccinia virus was prepared from material isolated from an equine, pox-lesion in Ankara (Turkey), that was serially passaged in excess of 570 times on primary chick embryo fibroblast cultures [25].…”