Selected Grantee Publications
Neutralizing Antibody Response to SARS‐CoV‐2 Bivalent mRNA Vaccine in SIV‐Infected Rhesus Macaques: Enhanced Immunity to XBB Subvariants by Two‐Dose Vaccination
Faraone, Journal of Medical Virology. 2024.
https://pubmed.ncbi.nlm.nih.gov/38528837/
Researchers have shown that mRNA vaccination is less effective for people with advanced or untreated HIV infection, but data on the efficacy of mRNA vaccination against SARS-CoV-2 in this population are limited. Using rhesus macaques (sex not specified) with simian immunodeficiency virus (SIV), investigators examined the neutralizing antibody (nAb) response to SARS-CoV-2 vaccination. They found that administration of the bivalent vaccine alone can generate robust nAb titers against Omicron subvariants. Additionally, dams that received antiretroviral therapy had lower nAb titers than untreated dams. Overall, these findings highlight the need for further investigations into the nAb response in people with HIV. Supported by ORIP (P51OD011104), NCI, NIAID, NICHD, and NIMH.
Deep Analysis of CD4 T Cells in the Rhesus CNS During SIV Infection
Elizaldi et al., PLOS Pathogens. 2023.
https://pubmed.ncbi.nlm.nih.gov/38060615/
Systemic HIV infection results in chronic inflammation that causes lasting damage to the central nervous system (CNS), despite long-term antiretroviral therapy (ART). Researchers studied neurocognitive outcomes in male and female rhesus macaques infected with simian immunodeficiency virus (SIV) using an ART regimen simulating suboptimal adherence; one group received no ART, and the other received ART with periodic interruptions. Using single-cell transcriptomic profiling, the researchers also identified molecular programs induced in the brain upon infection. They found that acute infection led to marked imbalance in the CNS CD4/CD8 T‑cell ratio, which persisted into the chronic phase. The studies provide insight into the role of CD4 T cells in the CNS during HIV infection. Supported by ORIP (P51OD011107, K01OD023034), NIA, NIAID, and NCI.
IL-21-IgFc Immunotherapy Alters Transcriptional Landscape of Lymph Node Cells Leading to Enhanced Flu Vaccine Response in Aging and SIV Infection
Pallikkuth et al., Aging Cell. 2023.
https://pubmed.ncbi.nlm.nih.gov/37712598/
Aging is associated with increased risk of seasonal flu disease burden and serious flu-related complications, particularly for people with HIV. In this study, investigators aimed to elucidate the immunomodulation following flu vaccination in aging male and female rhesus macaques infected with simian immunodeficiency virus (SIV). Their results suggest that IL-21 treatment at the time of flu vaccination modulates the inductive lymph node germinal center activity to reverse SIV-associated immune dysfunction. The authors identified IL-21 as a potential candidate molecule for immunotherapy to enhance flu vaccine responses in affected populations. Further studies could examine the overall benefit of IL-21 immunotherapy on mucosal lung immunity and protection against infection. Supported by ORIP (R24OD010947), NIA, and NIAID.
HIV, Asymptomatic STI, and the Rectal Mucosal Immune Environment Among Young Men Who Have Sex With Men
Van Doren et al., PLOS Pathogens. 2023.
https://www.doi.org/10.1371/journal.ppat.1011219
Young men who have sex with men (YMSM) are affected disproportionately by HIV and bacterial sexually transmitted infections (STIs) and therefore are likely to face an increased burden of associated chronic inflammation. Researchers studied the immunologic effects and interactions of HIV and bacterial STIs, as well as their effects on the rectal mucosal immune environment, among various populations of YMSM. Their findings suggest that asymptomatic bacterial STIs could contribute to inflammation, particularly among YMSM with HIV. This study provides insights into the immunopathogenesis of asymptomatic bacterial STIs and identifies a syndemic interaction between HIV and bacterial STIs in YMSM. Supported by ORIP (P51OD011132), NIAID, and NICHD.
Early Treatment Regimens Achieve Sustained Virologic Remission in Infant Macaques Infected with SIV at Birth
Wang et al., Nature Communications. 2022.
https://www.doi.org/10.1038/s41467-022-32554-z
About 150,000 children are infected postnatally with HIV each year. Early antiretroviral therapy (ART) in infants with HIV can reduce viral reservoir size, but ART-free virologic remission has not been achieved. The researchers hypothesized that proviral reservoir seeding in infants exposed to HIV might differ from that in adults. They characterized viral reservoirs in neonatal rhesus macaques of both sexes inoculated with simian immunodeficiency virus (SIV) at birth and given combination ART. The researchers reported that 9 months of treatment initiated at day 3 resulted in a sustained virologic remission, suggesting that early intervention with proper treatment regimens could be an effective strategy. Supported by ORIP (P51OD011104), NIAID, NICHD, and NIDCR.
Increased Proviral DNA in Circulating Cells Correlates With Plasma Viral Rebound in SIV-Infected Rhesus Macaques after Antiretroviral Therapy Interruption
Ziani et al., Journal of Virology. 2021.
https://jvi.asm.org/content/early/2021/01/05/JVI.02064-20
Investigators longitudinally tracked dynamic decay of cell-associated viral RNA/DNA in systemic and lymphoid tissues in SIV-infected rhesus macaques on prolonged combined antiretroviral therapy (cART) to evaluate predictors of viral rebound after treatment cessation. Suppressive cART substantially reduced plasma SIV RNA, cell-associated unspliced, and multiply spliced SIV RNA to undetectable levels, yet viral DNA remained detectable in systemic tissues and lymphoid compartments throughout cART. A rapid increase of integrated proviral DNA in peripheral mononuclear cells was detected once cART was withdrawn, accompanied by the emergence of detectable plasma viral load. The increase of peripheral proviral DNA post cART interruption correlated with the emergence and degree of viral rebound. These results suggest that measuring total viral DNA in SIV infection may be a relatively simple surrogate marker of reservoir size, and may predict viral rebound after treatment interruption, and inform treatment strategies. Supported by ORIP (P51OD011104), NIAID and NICHD.