Incomplete protection, but suppression of virus burden, elicited by subunit simian immunodeficiency virus vaccines

Abstract

We compared the efficacy of immunization with either simian immunodeficiency virus (SIV) Env glycoprotein (Env), Env plus Gag proteins (Gag-Env), or whole inactivated virus (WIV), with or without recombinant live vaccinia vector (VV) priming, in protecting 23 rhesus macaques (six vaccine and two control groups) from challenge with SIVmac251 clone BK28. Vaccination elicited high titers of syncytium-inhibiting and anti-Env (gp120/gpl60) antibodies in all vaccinated macaques and anti-Gag (p27) antibodies in groups immunized with WIV or Gag-Env. Only WIV-immunized macaques developed anticell (HuT78) antibodies. After homologous low-dose intravenous virus challenge, we used frequency of virus isolation, provirus burden, and change in antibody titers to define four levels of resistance to SIV infection as follows. (i) No infection ("sterilizing" immunity) was induced only in WIV-immunized animals. (ii) Abortive infection (strong immunity) was defined when virus or provirus were detected early in the postchallenge period but not thereafter and no evidence of virus or provirus was detected in terminal tissues. This response was observed in two animals (one W-Env and one Gag-Env). (iii) Suppression of infection (incomplete or partial immunity) described a gradient of virus suppression manifested by termination of viremia, declining postchallenge antibody titers, and low levels (composite mean = 9.1 copies per 106 cells) of provirus detectable in peripheral blood mononuclear cells or lymphoid tissues at termination (40 weeks postchallenge). This response occurred in the majority (8 of 12) of subunit-vaccinated animals. (iv) Active infection (no immunity) was characterized by persistent virus isolation from blood mononuclear cells, increasing viral antibody titers postchallenge, and high levels (composite mean = 198 copies per 106 cells) of provirus in terminal tissues and blood. Active infection developed in all controls and two of three W-Gag-Env-immunized animals. The results of this study restate the protective effect of inactivated whole virus vaccines produced in heterologous cells but more importantly demonstrate that a gradient of suppression of challenge virus growth, reflecting partial resistance to SIV infection, is induced by subunit vaccination. The latter finding may be pertinent to studies with human immunodeficiency virus vaccines, in which it is plausible that vaccination may elicit significant suppression of virus infection and pathogenicity rather than sterilizing immunity.

Studies of AIDS vaccination using an ex vivo feline immunodeficiency virus model: protection conferred by a fixed-cell vaccine against cell-free and cell-associated challenge differs in duration and is not easily boosted

“…Previous studies have shown that certain lentivirus-vaccinated hosts, although not fully protected, may nevertheless experience attenuated infections following challenge, as shown by reduced viral loads or delayed disease progression (1,17,18,22,26,31,46). In our study, there was little evidence that the initial p.v.…”

Simian immunodeficiency virus-specific cytotoxic T-lymphocyte induction through DNA vaccination of rhesus monkeys

“…However, these strategies have, in general, given disappointing results in primate protection studies. Immunization with regimens that include recombinant vaccinia virus or Mycobacterium bovis BCG constructs has not protected macaques against challenge with most simian immunodeficiency virus (SIV) isolates (1,4,(7)(8)(9)24). Novel vaccine strategies capable of eliciting HIV-1specific CTL should, therefore, be pursued.…”

Immunization of common marmosets with Epstein‐Barr virus (EBV) envelope glycoprotein gp340: Effect on viral shedding following EBV challenge

“…It is in the light of this that attempts to vaccinate against agents such as EBV, which become latent or establish persistence, should be viewed [Spring et al, 1996]. Successful vaccination against experimental lentivirus infection of primates has been reported in terms of delayed disease [Sutjipto et al, 1990], or by a gradient of suppression of growth of the challenge virus from sterilizing immunity to a decrease in virus or provirus burden [Israel et al, 1994]. In the context of primary infection with EBV, a decrease in virus replication following immunization may well prevent infectious mononucleosis in adolescence, and act to decrease the severity of disease in the EBV-negative recipients of a positive transplant.…”