Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV.
Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741-3752, 1996). This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS.
Ourmanov
I
I
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, USA.
Brown
C R
CR
Moss
B
B
Carroll
M
M
Wyatt
L
L
Pletneva
L
L
Goldstein
S
S
Venzon
D
D
Hirsch
V M
VM
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000276:immunology; D008253:Macaca mulatta; D008562:Membrane Glycoproteins; D011995:Recombination, Genetic; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*; D014759:Viral Envelope Proteins; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D015685:Fusion Proteins, gag-pol; C066594:Gag protein p27, Simian immunodeficiency virus; D015686:Gene Products, env; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; C087575:SIV envelope glycoprotein gp160; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C069623:gp120 protein, Simian immunodeficiency virus; C077410:simian immunodeficiency virus matrix protein p17