       Document 0197
 DOCN  M9440197
 TI    Incomplete protection, but suppression of virus burden, elicited by
       subunit simian immunodeficiency virus vaccines.
 DT    9404
 AU    Israel ZR; Edmonson PF; Maul DH; O'Neil SP; Mossman SP; Thiriart C;
       Fabry L; Van Opstal O; Bruck C; Bex F; et al; Department of Pathology,
       College of Veterinary Medicine and; Biomedical Sciences, Colorado State
       University, Fort Collins; 80523.
 SO    J Virol. 1994 Mar;68(3):1843-53. Unique Identifier : AIDSLINE
       MED/94149880
 AB    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/gp160) 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 VV-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 10(6) 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 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 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.
 DE    Animal  Antibodies, Viral/BLOOD  Base Sequence  Blood/MICROBIOLOGY
       Cells, Cultured  Comparative Study  Gene Products,
       gag/GENETICS/IMMUNOLOGY  Human  HIV Envelope Protein
       gp120/GENETICS/IMMUNOLOGY  Immunization, Secondary  *Immunotherapy,
       Active  Lymphocyte Transformation  Macaca mulatta  Molecular Sequence
       Data  Neutralization Tests  Proviruses/ISOLATION & PURIF  Recombinant
       Proteins/IMMUNOLOGY  Simian Acquired Immunodeficiency
       Syndrome/IMMUNOLOGY/PATHOLOGY/  *PREVENTION & CONTROL  Support, U.S.
       Gov't, P.H.S.  SIV/GROWTH & DEVELOPMENT  *Vaccination  *Vaccines,
       Synthetic  Vaccinia Virus/GENETICS  *Viral Vaccines  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

