Development of a tier 1 R5 clade C simian-human immunodeficiency virus as a tool to test neutralizing antibody-based immunoprophylaxis.
BACKGROUND
While some recently transmitted HIV clade C (HIV-C) strains exhibited tier 1 neutralization phenotypes, most were tier 2 strains (J Virol 2010; 84:1439). Because induction of neutralizing antibodies (nAbs) through vaccination against tier 2 viruses has proven difficult, we have generated a tier 1, clade C simian-human immunodeficiency virus (SHIV-C) to permit efficacy testing of candidate AIDS vaccines against tier 1 viruses.


METHODS
SHIV-1157ipEL was created by swapping env of a late-stage virus with that of a tier 1, early form.


RESULTS
After adaptation to rhesus macaques (RM), passaged SHIV-1157ipEL-p replicated vigorously in vitro and in vivo while maintaining R5 tropism. The virus was reproducibly transmissible intrarectally. Phylogenetically, SHIV-1157ipEL-p Env clustered with HIV-C sequences. All RM chronically infected with SHIV-1157ipEL-p developed high nAb titers against autologous as well as heterologous tier 1 strains.


CONCLUSIONS
SHIV-1157ipEL-p was reproducibly transmitted in RM, induced cross-clade nAbs, and represents a tool to evaluate anti-HIV-C nAb responses in primates.
Dana-Farber Cancer Institute, Boston, MA 02115, USA. nb_siddappa@dfci.harvard.edu
Nagadenahalli B
NB
Siddappa
Girish
G
Hemashettar
Yin Ling
YL
Wong
Samir
S
Lakhashe
Robert A
RA
Rasmussen
Jennifer D
JD
Watkins
Francis J
FJ
Novembre
François
F
Villinger
James G
JG
Else
David C
DC
Montefiori
Ruth M
RM
Ruprecht
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D015752:Genes, env; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology*; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing