Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge.
An effective human immunodeficiency virus (HIV) vaccine will likely need to reduce mucosal transmission and, if infection occurs, control virus replication. To determine whether our best simian immunodeficiency virus (SIV) vaccine can achieve these lofty goals, we vaccinated eight Indian rhesus macaques with SIVmac239Delta nef and challenged them intrarectally (i.r.) with repeated low doses of the pathogenic heterologous swarm isolate SIVsmE660. We detected a significant reduction in acquisition of SIVsmE660 in comparison to that for naïve controls (log rank test; P = 0.023). After 10 mucosal challenges, we detected replication of the challenge strain in only five of the eight vaccinated animals. In contrast, seven of the eight control animals became infected with SIVsmE660 after these 10 challenges. Additionally, the SIVsmE660-infected vaccinated animals controlled peak acute virus replication significantly better than did the naïve controls (Mann-Whitney U test; P = 0.038). Four of the five SIVsmE660 vaccinees rapidly brought virus replication under control by week 4 postinfection. Unfortunately, two of these four vaccinated animals lost control of virus replication during the chronic phase of infection. Bulk sequence analysis of the circulating viruses in these animals indicated that recombination had occurred between the vaccine and challenge strains and likely contributed to the increased virus replication in these animals. Overall, our results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication.
Reynolds
Matthew R
MR
AIDS Vaccine Research Laboratory, 555 Science Dr., Madison, WI 53711, USA. mrreynol@wisc.edu
Weiler
Andrea M
AM
Piaskowski
Shari M
SM
Kolar
Holly L
HL
Hessell
Ann J
AJ
Weiker
Madelyn
M
Weisgrau
Kim L
KL
León
Enrique J
EJ
Rogers
W Eric
WE
Makowsky
Robert
R
McDermott
Adrian B
AB
Boyle
Rosanne
R
Wilson
Nancy A
NA
Allison
David B
DB
Burton
Dennis R
DR
Koff
Wayne C
WC
Watkins
David I
DI
D000818:Animals; D008253:Macaca mulatta; D011995:Recombination, Genetic; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000517:prevention & control
D018449:SAIDS Vaccines