Selected Grantee Publications
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- 151 results found
- Immunology
- P51
Antimicrobial Prophylaxis Does Not Improve Post-Surgical Outcomes in SIV/SHIV–Uninfected or SIV/SHIV–Infected Macaques (Macaca mulatta and Macaca fascicularis) Based on a Retrospective Analysis
Moats et al., PLOS One. 2022.
https://www.doi.org/10.1371/journal.pone.0266616
Some institutions routinely administer antimicrobial prophylaxis to nonhuman primates prior to surgery to prevent surgical site infections. In this study, the investigators assessed the influence of antimicrobial prophylaxis on complication rates in macaques of both sexes receiving peripheral lymph node (PLN) and laparoscopic biopsies. After PLN biopsies, no significant differences were observed between animals that received antimicrobial prophylaxis and those that did not. After laparoscopic biopsies, complication rates were greater in animals that received antimicrobial prophylaxis. Because of these findings, the authors recommend eliminating the use of unnecessary antibiotics in research animals. Supported by ORIP (U42OD023038, P51OD011092).
Early Post-Vaccination Gene Signatures Correlate With the Magnitude and Function of Vaccine-Induced HIV Envelope–Specific Plasma Antibodies in Infant Rhesus Macaques
Vijayan et al., Frontiers in Immunology. 2022.
https://www.doi.org/10.3389/fimmu.2022.840976
An effective vaccine is needed to reduce HIV infections, particularly among younger people. The initiation of an HIV vaccine regimen in early life could allow the development of mature HIV‑specific antibody responses that protect against infection. The investigators compared the effects of two vaccine regimens in infant rhesus macaques (sex not specified). Both vaccines induced a rapid innate response, indicated by elevated inflammatory plasma cytokines and altered gene expression. By performing a network analysis, the investigators identified differentially expressed genes associated with B cell activation. These findings suggest that vaccine-induced immunity can be optimized by modulating specific antibody and T cell responses. Supported by ORIP (P51OD011107), NCI, NIAID, and NIDCR.
A Potent Myeloid Response Is Rapidly Activated in the Lungs of Premature Rhesus Macaques Exposed to Intra-Uterine Inflammation
Jackson et al., Mucosal Immunology. 2022.
https://www.doi.org/10.1038/s41385-022-00495-x
Up to 40% of preterm births are associated with histological chorioamnionitis (HCA), which can lead to neonatal mortality, sepsis, respiratory disease, and neurodevelopmental problem. Researchers used rhesus macaques to comprehensively describe HCA-induced fetal mucosal immune responses and delineate the individual roles of IL-1β and TNFα in HCA-induced fetal pathology. Their data indicate that the fetal innate immune system can mount a rapid, multifaceted pulmonary immune response to in utero exposure to inflammation. Taken together, this work provides mechanistic insights into the association between HCA and the postnatal lung morbidities of the premature infant and highlights the therapeutic potential of inflammatory blockade in the fetus. Supported by ORIP (P51OD011107), NIEHS, NIDDK, NHLBI, and NICHD.
Presence of Natural Killer B Cells in Simian Immunodeficiency Virus–Infected Colon That Have Properties and Functions Similar to Those of Natural Killer Cells and B Cells but Are a Distinct Cell Population
Cogswell et al., mSphere. 2022.
https://www.doi.org/10.1128/jvi.00235-22
HIV infection of the gut is associated with increased mucosal inflammation, and the role of natural killer B (NKB) cells in this process requires further investigation. In this study, the researchers used rhesus and cynomolgus macaque models to characterize the function and characteristics of NKB cells in response to simian immunodeficiency virus (SIV) infection. They reported that NKB cells can kill target cells, proliferate, and express several inflammatory cytokines. The properties of NKB cells could provide insight into the inflammation observed in the gut during SIV infection, and the individual contributions of each cytokine and receptor–ligand interaction could be explored in a future study. Supported by ORIP (P51OD011106), NIAID, and NIGMS.
Phagocytosis by an HIV Antibody Is Associated with Reduced Viremia Irrespective of Enhanced Complement Lysis
Spencer et al., Nature Communications. 2022.
https://doi.org/10.1038/s41467-022-28250-7
Researchers used the bNAb 10E8v4 targeting the HIV Env protein to examine the role of antibody-mediated effector and complement (C′) activity when 10E8v4 was administered prophylactically to rhesus monkeys challenged with simian-human immunodeficiency virus (SHIV). With sub-protective dosing, the researchers found a 78–88% reduction in post-acute viremia that was associated with 10E8v4–mediated phagocytosis. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to therapeutic efficacy against SHIV, while C′ functions do not contribute to efficacy in this context. This research informs the design of bNAb modifications for improving the protective efficacy of this therapeutic approach against HIV. Supported by ORIP (P51OD011092, U42OD023038) and NIAID.
Vaccine-Induced, High-Magnitude HIV Env-Specific Antibodies with Fc-Mediated Effector Functions Are Insufficient to Protect Infant Rhesus Macaques against Oral SHIV Infection
Curtis et al., mSphere. 2022.
https://www.doi.org/10.1128/msphere.00839-21
A tailored, effective HIV vaccine is needed to prevent mother-to-child viral transmission. In nonhuman primate models, infection with simian–human immunodeficiency virus (SHIV) can be prevented by administering broadly neutralizing HIV envelope (Env)–specific antibodies. Investigators tested the efficacy of an intramuscular vaccine regimen against SHIV infection in male and female infant rhesus macaques. The vaccine induced Env-specific antibodies in plasma, with antibody-dependent cellular cytotoxicity and phagocytic function. These antibodies, however, were insufficient for protection against infection. Future studies could focus on improving the breadth of antibody response and improving cell-mediated immunity. Supported by ORIP (P51OD011107), NCI, NIAID, and NIDCR.
CAR/CXCR5–T Cell Immunotherapy Is Safe and Potentially Efficacious in Promoting Sustained Remission of SIV Infection
Pampusch et al., PLOS Pathogens. 2022.
https://www.doi.org/10.1371/journal.ppat.1009831
HIV and simian immunodeficiency virus (SIV) replication are concentrated within the B cell follicles of secondary lymphoid tissues. In this study, the researchers developed immunotherapeutic chimeric antigen receptor (CAR) T cells that home to follicles and clear SIV-infected cells in a rhesus macaque model. The CAR T cells localized to the follicle, replicated, and interacted directly with infected cells. Most of the treated animals maintained lower viral loads in the blood and follicles, compared to control animals. These findings demonstrate the safety and potential efficacy of this immunotherapy approach for long-term remission of HIV without requiring the lifelong use of antiretroviral therapy. Supported by ORIP (P51OD011106), NIAID, and NHLBI.
Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006–2011)
Balinda et al., Viruses. 2022.
https://www.doi.org/10.3390/v14020334
About 80 percent of heterosexual HIV-1 transmission events are thought to be attributable to a single transmitted/founder (T/F) virus. Studies of HIV T/F viruses could yield valuable insights on transmission and help inform the design of vaccines and therapeutics. To date, most T/F studies have focused on subtype B and C viruses; few studies have focused on subtype D. In this study, the researchers characterized near full-length T/F viral genomes to identify subtype D and A/D recombinants from heterosexual mucosal transmissions in humans. They reported high viral diversity and high pathogenicity, underscoring the importance of matching vaccine designs to the predominant subtypes within populations. Further studies of the full genome sequence could provide additional information for subtyping. Supported by ORIP (P51OD011132) and NIAID.
Simian Immunodeficiency Virus Infection Mediated Changes in Jejunum and Peripheral SARS-CoV-2 Receptor ACE2 and Associated Proteins or Genes in Rhesus Macaques
Boby et al., Frontiers in Immunology. 2022.
https://www.doi.org/10.3389/fimmu.2022.835686
Recent studies suggest that people with HIV—particularly those not receiving antiretroviral therapy or those with low CD4 cell counts—are at increased risk of severe illness from SARS‑CoV-2 coinfection. Angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2, is likely to play an important role in modulating physiological and pathological events during HIV infection. In this study, the researchers used a rhesus macaque model to characterize the expression profiles of ACE2, other renin-angiotensin system (RAS)–associated genes (AGTR1/2, ADAM17, and TMPRSS2), and inflammatory cytokines (IL-1β, IL-6, and TNF‑α) in the jejunum and lung during simian immunodeficiency virus (SIV) infection. SIV infection was associated with multiple changes in gene expression, including downregulation of ACE2, which could lead to loss of gut homeostasis. Further studies could provide insight on the role of RAS-associated proteins during HIV and SARS-CoV-2 co-infection. Supported by ORIP (P51OD011104) and NIDDK.
Expression, Activity, and Regulation of Phosphorylating Enzymes in Tissues and Cells Relevant to HIV-1 Sexual Transmission
Hu et al., AIDS Research and Human Retroviruses. 2022.
https://www.doi.org/10.1089/AID.2020.0250
Phosphorylating enzymes (PEs) are critical for activating nucleoside/nucleotide reverse transcriptase inhibitors (e.g., tenofovir [TFV]), but limited information is available about the expression of PEs in the female genital tract and colon tissue. Investigators compared the mRNA expression of seven PEs involved in metabolism of TFV in cervicovaginal and colon tissues. This work involved human, pigtailed macaque, and rabbit tissues; human cervicovaginal epithelial cell lines; T cell lines; and primary CD4+ T cells. Taken together, this study suggests that TFV activation differs among immune cells and local tissues under varying conditions. Additionally, the variability of PE expression levels found across species provides critical information to assist with the interpretation of data obtained using these animal models. Supported by ORIP (P51OD010425) and NIAID.