Protection against lethal simian immunodeficiency virus SIVsmmPBj14 disease by a recombinant Semliki Forest virus gp160 vaccine and by a gp120 subunit vaccine.
Infection of pigtail macaques with SIVsmmPBj14, biological clone 3 (SIV-PBj14-bc13), produces an acute and usually fatal shock-like syndrome 7 to 14 days after infection. We used this simian immunodeficiency virus (SIV) model as a rapid and rigorous challenge to evaluate the efficacy of two SIV Env vaccine strategies. Groups of four pigtail macaques were immunized four times over a 25-week span with either a recombinant Semliki Forest virus expressing the SIV-PBj14 Env gp160 (SFV-SIVgp160) or purified recombinant SIV-PBj14 gp120 (rgp120) in SBN-1 adjuvant. Antibody titers to SIV Env developed in all immunized animals (mean peak titers prior to challenge, 1:1,700 for SFV-SIV gp 160 and 1:10,500 for rgp120), but neither neutralizing antibodies nor SIV-specific T-cell proliferative responses were detectable in any of the vaccinees. All macaques were challenged with a 100% infectious, 75% fatal dose of SIV-PBj14-bc13 at week 26. Three of four control animals died of acute SIV-PBj14 syndrome on days 12 and 13. By contrast, all four SFV-SIVgp160-immunized animals and three of the four rgp120-immunized animals were protected from lethal disease. While all virus-challenged animals became infected, symptoms of the SIV-PBj14 syndrome were more severe in controls than in vaccinees. Mean virus titers in plasma at 13 days postchallenge were approximately 10-fold lower in vaccinated than control animals. However, there was no apparent correlation between survival and levels of peripheral blood mononuclear cell-associated culturable virus, provirus load, or any antiviral immunologic parameter examined. The results indicate that while immunization with SFV-SIVgp160 and rgp120 did not protect against virus infection, these Env vaccines did lower the virus load in plasma and protect against the lethal SIV-PBj14 challenge.
Mossman
S P
SP
Department of Pathology, Colorado State University, Fort Collins 80523, USA.
Bex
F
F
Berglund
P
P
Arthos
J
J
O'Neil
S P
SP
Riley
D
D
Maul
D H
DH
Bruck
C
C
Momin
P
P
Burny
A
A
Fultz
P N
PN
Mullins
J I
JI
Liljeström
P
P
Hoover
E A
EA
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D004279:DNA, Viral; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008254:Macaca nemestrina; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D018449:SAIDS Vaccines / Q000276:immunology*; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000401:mortality / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000254:growth & development / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins
D000914:Antibodies, Viral; D004279:DNA, Viral; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; C087575:SIV envelope glycoprotein gp160; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus