IL-21-IgFc Immunotherapy Alters Transcriptional Landscape of Lymph Node Cells Leading to Enhanced Flu Vaccine Response in Aging and SIV Infection
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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.
Cytomegalovirus Infection Facilitates the Costimulation of CD57+CD28- CD8 T Cells in HIV Infection and Atherosclerosis via the CD2–LFA-3 Axis
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People with HIV are at increased risk of developing atherosclerosis and other cardiovascular diseases, and HIV coinfection with cytomegalovirus (CMV) is associated with immune activation and inflammation. In this study, researchers explored the role of the CD2–LFA-3 axis in driving activation and proliferation of CD57+CD28- CD8 T cells using clinical samples from patients with or without HIV.
Intradermal but Not Intramuscular Modified Vaccinia Ankara Immunizations Protect Against Intravaginal Tier2 Simian–Human Immunodeficiency Virus Challenges in Female Macaques
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Researchers have been exploring multiple strategies to develop an HIV vaccine. In this study, the investigators determined the immunogenicity and efficacy of intradermal and intramuscular routes of modified vaccinia Ankara (MVA) vaccination in female rhesus macaques. They found that both routes of MVA vaccination enabled control of viral replication, but only the intradermal vaccination was effective in protection against viral acquisition. Their findings suggest that the intradermal MVA vaccinations provide protection by modulating the innate and T helper responses.
Host Immunity Associated With Spontaneous Suppression of Viremia in Therapy-Naïve Young Rhesus Macaques Following Neonatal SHIV Infection
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Previously, investigators developed a pediatric rhesus macaque model for simian–human immunodeficiency virus infection that can be exploited to identify host immunity associated with viremia suppression. In the present study, they used the model (with male and female animals) to characterize humoral and cellular immunity and plasma biomarkers associated with spontaneous viremia suppression. They identified CD8-expressing cells and varied T-cell subsets that were associated with viremia suppression.
Conjugation of HIV-1 Envelope to Hepatitis B Surface Antigen Alters Vaccine Responses in Rhesus Macaques
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Researchers are interested in developing an HIV-1 vaccine that improves upon the regimen used in the RV144 clinical trial. The authors tested the hypothesis that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T-cell help and improve antibody production against HIV-1. Using juvenile rhesus macaques of both sexes, they evaluated the immunogenicity of their conjugate regimen.
A Combined Adjuvant Approach Primes Robust Germinal Center Responses and Humoral Immunity in Non-Human Primates
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Protein antigens require adjuvants for high immunogenicity, and delivery kinetics are a critical component of rational HIV vaccine design. Investigators employed a combined adjuvant approach (i.e., short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide, plus saponin/MPLA nanoparticles) with slow antigen delivery and potent immune-stimulating complexes in rhesus macaques of both sexes. They reported that pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells.
Intravenous Bacille Calmette–Guérin Vaccination Protects Simian Immunodeficiency Virus–Infected Macaques From Tuberculosis
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People with HIV are susceptible to developing tuberculosis and experiencing associated complications. Researchers assessed the safety, immunogenicity, and efficacy of intravenous Bacille Calmette–Guérin vaccination in male and female cynomolgus macaques coinfected with simian immunodeficiency virus (SIV) and Mycobacterium tuberculosis. The vaccine conferred protection in all vaccinated SIV-naive animals and in 9 of 12 vaccinated SIV-infected animals. These data suggest that the vaccine is immunogenic and efficacious in SIV-infected animals.
HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing
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Current HIV treatment strategies are focused on forced proviral reactivation and elimination of reactivated cells with immunological or toxin-based technologies. Researchers have proposed the use of a novel “block-lock-stop” approach, which entails the long-term durable silencing of viral expression and permanent transcriptional deactivation of the latent provirus. In the present study, the authors present this approach and its rationale.
High Throughput Analysis of B Cell Dynamics and Neutralizing Antibody Development During Immunization With a Novel Clade C HIV-1 Envelope
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Broadly neutralizing antibodies from chronic infection are an area of interest for HIV-1 vaccine development. Using male and female rhesus macaques, a team of researchers conducted a high-throughput longitudinal study to determine how B cells respond to vaccines expressing different HIV-1 Env immunogens. In most animals, the B cells failed to achieve neutralizing activity. One animal, however, developed neutralizing antibodies against the vaccine strain. These data suggest that early elicitation might favor the induction of neutralizing antibodies against HIV-1 Env.
CD8+ T Cells Control SIV Infection Using Both Cytolytic Effects and Non-Cytolytic Suppression of Virus Production
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HIV continuously evades and subdues the host immune responses through multiple strategies, and an understanding of these strategies can help inform research efforts. Using a mathematical model, investigators assessed whether CD8+ cells from male rhesus macaques exert a cytolytic response against infected cells prior to viral production. Their goal was to elucidate the possible mode of action of CD8+ cells on simian immunodeficiency virus (SIV)–infected cells.