Efficacy of a multigenic protein vaccine containing multimeric HIV gp160 against heterologous SHIV clade C challenges.
OBJECTIVE
To determine whether multigenic protein immunogens including native, trimeric HIV clade C (HIV-C) gp160 could cross-protect macaques against mucosal challenge with clade C (SHIV-C) mismatched for env.


METHODS
Because AIDS vaccine recipients are unlikely to encounter exactly matched HIV strains and to represent the diversity of locally circulating HIV-C strains, we selected env genes to generate the gp160 immunogen and SHIV-C from different, recently infected infants of the same clinical cohort in Zambia. In a model of postnatal HIV-C transmission, infant macaques were immunized with soluble viral proteins, including trimeric HIV1084i Env, and challenged with SHIV-1157ip; protein-only vaccination was compared with a DNA prime/protein boost strategy.


METHODS
All vaccinated and control monkeys were exposed orally to low-dose, R5-tropic SHIV-1157ip encoding heterologous env. Animals with no or only transient infection were rechallenged intrarectally with a high dose of R5 SHIV-1157ipd3N4, a 'late', animal-evolved SHIV-1157ip variant. Animals were followed prospectively for immune parameters and viral RNA loads.


RESULTS
Vaccination induced cross-neutralizing antibodies. Compared to controls, vaccinees had significantly lower peak viral RNA loads, and one vaccine recipient remained completely virus-free, even in lymphoid tissues. There was a trend for the protein-only vaccine to yield better protection than the combined modality approach.


CONCLUSIONS
Protein-only immunogens induced significant protection against heterologous viruses encoding env from locally circulating viruses.
Rasmussen
Robert A
RA
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Ong
Helena
H
Song
Ruijiang
R
Chenine
Agnès-Laurence
AL
Ayash-Rashkovsky
Mila
M
Hu
Shiu-Lok
SL
Polacino
Patricia
P
Else
James G
JG
Novembre
Francis J
FJ
Ruprecht
Ruth M
RM
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D004279:DNA, Viral / Q000276:immunology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D015683:Gene Products, gag / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D012367:RNA, Viral / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology
D000914:Antibodies, Viral; D004279:DNA, Viral; D015683:Gene Products, gag; D015696:Gene Products, tat; D019302:HIV Envelope Protein gp160; D012367:RNA, Viral; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins