INCOMPLETE PROTECTION, BUT SUPPRESSION OF VIRUS BURDEN, ELICITED BY SUBUNIT SIMIAN IMMUNODEFICIENCY VIRUS-VACCINES

We compared the efficacy of immunization with either simian immunodefi ciency virus (SIV) Env glycoprotein (Env), Env plus Gag proteins (Gag- Env), or whole inactivated virus (WIV), with or without recombinant li ve vaccinia vector (VV) priming, in protecting 23 rhesus macaques (six vaccine and two control groups) from challenge with SIVmac251 clone B K28. Vaccination elicited high titers of syncytium-inhibiting and anti -Env (gp120/gp160) antibodies in all vaccinated macaques and anti-Gag (p27) antibodies in groups immunized with WIV or Gag-Env. Only WIV-imm unized macaques developed anticell (HuT78) antibodies. After homologou s low-dose intravenous virus challenge, we used frequency of virus iso lation, provirus burden, and change in antibody titers to define four levels of resistance to STV 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;provi rus 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 VV-Env and one Gag-En v). (iii) Suppression of infection (incomplete or partial immunity) de scribed a gradient of virus suppression manifested by termination of v iremia, declining postchallenge antibody titers, and low levels (compo site mean = 9.1 copies per 10(6) cells) of provirus detectable in peri pheral 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) wa s characterized by persistent virus isolation from blood mononuclear c ells, increasing viral antibody titers postchallenge, and high levels (composite mean = 198 copies per 10(6) cells) of provirus in terminal tissues and blood. Active infection developed in all controls and two of three VV-Gag-Env-immunized animals. The results of this study resta te 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 resistan ce to SIV infection, is induced by subunit vaccination. The latter fin ding may be pertinent to studies with human immunodeficiency virus vac cines, in which it is plausible that vaccination may elicit significan t suppression of virus infection and pathogenicity rather than sterili zing immunity.