Abstract
Rhesus macaques can be readily infected with chimeric simian-human immunodeficiency viruses (SHIV) as a suitable virus challenge system for testing the efficacy of HIV vaccines. Three Chinese-origin rhesus macaques (ChRM) were inoculated intravenously (IV) with SHIVC109P4 in a rapid serial in vivo passage. SHIV recovered from the peripheral blood of the final ChRM was used to generate a ChRM-adapted virus challenge stock. This stock was titrated for the intrarectal route (IR) in 8 ChRMs using undiluted, 1:10 or 1:100 dilutions, to determine a suitable dose for use in future vaccine efficacy testing via repeated low-dose IR challenges. All 11 ChRMs were successfully infected, reaching similar median peak viraemias at 1–2 weeks post inoculation but undetectable levels by 8 weeks post inoculation. T-cell responses were detected in all animals and Tier 1 neutralizing antibodies (Nab) developed in 10 of 11 infected ChRMs. All ChRMs remained healthy and maintained normal CD4+ T cell counts. Sequence analyses showed >98% amino acid identity between the original inoculum and virus recovered at peak viraemia indicating only minimal changes in the env gene. Thus, while replication is limited over time, our adapted SHIV can be used to test for protection of virus acquisition in ChRMs.
Highlights
SHIVC109P4 was adapted for replication in Chinese-origin rhesus macaques (ChRM) via 3 rapid in vivo serial animal-to-animal passages (Figure 1a)
This study succeeded in generating a ChRM-adapted simian-human immunodeficiency viruses (SHIV) inoculum through in vivo serial passages that was titrated in vivo to determine a dose suitable for use in repeated low-dose intrarectal challenges in future HIV vaccine efficacy studies
This study demonstrated the feasibility of developing local research capacity to conduct preclinical evaluations of vaccine efficacy and the potential of accelerating HIV vaccine development in South Africa
Summary
Despite the reported steady global decline of deaths caused by HIV, the number of new infections continues to be unacceptably high and the only cost-effective measure to curb this trend remains a protective vaccine. Nonhuman primate (NHP) models have gained prominence based on their close physiology and immune setup to man and the availability of lentiviruses that are able to infect NHPs and cause pathology. Persistence of these viruses in NHP hosts even after prolonged antiretroviral treatments have led to a vigorous effort to investigate HIV cure in these models [1,2]. Infection of rhesus macaques (RM) with pathogenic chimeric viruses, simian-human immunodeficiency viruses (SHIVs) containing an increasing number of HIV-1 env genes, have been shown to induce simian AIDS [3], though less readily than the more virulent
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