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.
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.
Metabolic Transitions Define Spermatogonial Stem Cell Maturation
Voigt et al., Human Reproduction. 2022.
https://www.doi.org/10.1093/humrep/deac157
The spermatogonial stem cell (SSC) is the basis of male fertility. One potential option to preserve fertility in patients treated with anti-cancer therapy is isolation and laboratory culture of the juvenile SSC pool with subsequent transplantation to restore spermatogenesis. However, efficient culture of undifferentiated spermatogonia, including SSCs, in mammals other than rodents remains challenging. Investigators reported that the metabolic phenotype of prepubertal human spermatogonia is distinct from that of adult spermatogonia and that SSC development is characterized by specific metabolic transitions from oxidative phosphorylation to anaerobic metabolism. Supported by ORIP (R01OD016575) 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.
Postpubertal Spermatogonial Stem Cell Transplantation Restores Functional Sperm Production in Rhesus Monkeys Irradiated Before and After Puberty
Shetty et al., Andrology. 2021.
https://onlinelibrary.wiley.com/doi/10.1111/andr.13033
Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). Prepubertal rhesus monkeys (n=6) were unilaterally castrated, and the remaining testes irradiated twice to insure loss of SSCs; the animals were treated with a vehicle or GnRH antagonist for 8 weeks (n=3/treatment). The cryopreserved prepubertal testicular tissue was allergenically transplanted into the intact testes of the monkeys after puberty. Recovery of viable donor epididymal sperm was observed in half the monkeys. These results illustrate that sperm production can be restored in primates by transplantation of testicular cells from cryopreserved untreated prepubertal testes into seminiferous tubules of the remaining testes. Supported by ORIP (P51OD011092), NICHD, and NCI.
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.