Abstract
BackgroundSimian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines. These studies frequently utilize high-doses of SIV that ensure infection after a single challenge but do not recapitulate critical facets of sexual HIV transmission. Investigators are increasingly using low-dose challenges in which animals are challenged once every week or every two weeks in order to better replicate sexual HIV transmission. Using this protocol, some animals require over ten challenges before SIV infection is detectable, potentially inducing localized immunity. Moreover, the lack of certainty over which challenge will lead to productive infection prevents tissue sampling immediately surrounding the time of infection.FindingsHere we challenged Mauritian cynomolgus macaques with 100 50% tissue culture infectious doses (TCID50) of SIVmac239 intrarectally three times a day for three consecutive days. Ten of twelve animals had positive plasma viral loads after this challenge regimen.ConclusionsThis approach represents a straightforward advance in SIV challenge protocols that may avoid induction of local immunity, avoid inconsistent timing between last immunization and infection, and allow sampling immediately after infection using low-dose challenge protocols.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-014-0066-z) contains supplementary material, which is available to authorized users.
Highlights
Simian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines
This approach represents a straightforward advance in SIV challenge protocols that may avoid induction of local immunity, avoid inconsistent timing between last immunization and infection, and allow sampling immediately after infection using low-dose challenge protocols
Developing both cures and vaccines for HIV requires a clear understanding of early events after infection when HIV seeds the latent reservoir and decimates the mucosal immune system; it is nearly impossible to determine, with certainty, the sequence of the infecting virus or exactly when an individual was infected
Summary
Simian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines. We developed a protocol to challenge animals intrarectally with a low-dose of SIV multiple times in a short duration, an approach termed “rapid, repeated, low-dose” infection (RRLD). These viral loads are comparable to Mauritian cynomolgus macaques challenged with SIV with a single high-dose of SIV (Figure 1 and Data not shown).
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