Effect of vaccination with recombinant modified vaccinia virus Ankara expressing structural and regulatory genes of SIV_macJ5 on the kinetics of SIV replication in cynomolgus monkeys

Abstract

The efficacy of a multicomponent vaccination with modified vaccinia Ankara constructs (rMVA) expressing structural and regulatory genes of simian immunodeficiency virus (SIV(mac251/32H/J5)) was investigated in cynomolgus monkeys, following challenge with a pathogenic SIV. Vaccination with rMVA-J5 performed at week 0, 12, and 24 induced a moderate proliferative response to whole SIV, a detectable humoral response to all but Nef SIV antigens, and failed to induce neutralizing antibodies. Two months after the last boost, the monkeys were challenged intravenously with 50 MID50 of SIV(mac251). All control monkeys, previously inoculated with non-recombinant MVA, were infected by week two and seroconverted by weeks four to eight. In contrast a sharp increase of both humoral and proliferative responses at two weeks post-challenge was observed in vaccinated monkeys compared to control monkeys. Although all vaccinated monkeys were infected, vaccination with rMVA-J5 appeared to partially control viral replication during the acute and late phase of infection as judged by cell- and plasma-associated viral load.

Immunological responses and viral modulatory effects of vaccination with recombinant modified vaccinia virus Ankara (rMVA) expressing structural and regulatory transgenes of simian immunodeficiency virus (SIVmac32H/J5M)

“…The overall outcome of this study reflects similar observations using the same vaccines and immunization protocol [36]. Even when the combination of rSFV priming and rMVA boosting was demonstrated to elicit more potent immune responses [37] there was no specific benefit following mucosal challenge with a heterologous virus stock.…”

“…However, T‐cell proliferative responses were measured at the day of challenge, although across all groups these were all at low or undetectable levels. Limited serological and cellular anti‐gag responses have been observed by others in this multi‐centre study [36, 37, 42], although are improved if primed with a heterologous viral vector (rSFV) expressing the homologous Gag insert [37]. Hence, whilst effective immunization against Gag protein was possible with this rMVA construct, levels of Gag protein expression appear to be intrinsically low.…”

“…Similar reductions in the frequency of virus‐infected cells in the periphery were also observed. Another study using this vaccine also reported a temporary reduction in both measures of virus load that occurred simultaneously [36]. However, there was no link between any broad‐based SIV‐specific immunity as a result of simultaneous inoculation of multiple MVA vaccination expressing different SIV transgenes with enhanced or sustained control of virus replication.…”

“…The goal was to analyse the capacity of pox‐virus vaccination approaches to protect against homologous and heterologous SIV challenge via mucosal and parenteral routes. Aspects of this multi‐centre study have been reported previously [36, 37, 42]. The specific aims of this study were to evaluate immune responses and protective efficacy conferred by three immunizations with MVA vectors that expressed five different SIV transgenes, or two immunizations with these same vectors followed by a boost with fixed inactivated SIV‐infected simian cells in a manner analogous with that described by Hirsch et al.…”

Seasonal changes in the seminiferous epithelium of rhesus and bonnet monkeys

“…A majority of scientists accept the need for nonhuman primates in biomedical research due to phylogenetic closeness. Recently primates have been used as a model for pathogenicity, PET camera drug analysis, debilitating infections with high morbidity/mortality, HIV infection and its vaccination strategies [15,16,23,29,36] as well as in screening of various anti-spermatogenic/antitesticular agents [26,34]. As circannual variations have been reported in different species of monkeys with regard to testicular endocrine and exocrine functions that indicate distinct seasonality in the testicular volume/size, sperm production, semen quality, sexual behavior and hormonal [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone) milieu -having maximal responses during the breeding season followed by a period of sexual quiescence [25,28,30,40,42], the relevance of such studies remain unexplained in non-human primate species [10,21,27,42,43].…”