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MedRxiv : the Preprint Server For... May 2024Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies...
UNLABELLED
Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding and immunogenicity in a first-in-healthy adult (n=17), randomized, placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, B-cell and CD4+ T-cell responses emerged post-vaccination. Five vaccinees developed serum autologous tier-2 nAbs (ID50 titer, 1:28-1:8647) after 2-3 doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B-cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.
KEY TAKEAWAY/TAKE-HOME MESSAGES
HIV BG505 SOSIP.664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched clade A, tier 2 virus, that map to diverse Env epitopes with relatively high titers. The novel adjuvant may be an important mediator of vaccine response.
PubMed: 38766048
DOI: 10.1101/2024.05.08.24306957 -
Cell Jun 2024A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with...
A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.
Topics: Humans; AIDS Vaccines; HIV-1; Antibodies, Neutralizing; B-Lymphocytes; HIV Antibodies; HIV Infections; Cell Lineage; Liposomes; env Gene Products, Human Immunodeficiency Virus; Mutation; HIV Envelope Protein gp41
PubMed: 38761800
DOI: 10.1016/j.cell.2024.04.033 -
Scientific Reports May 2024Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime...
Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.
Topics: Humans; Qatar; Hepatitis B; Female; Transients and Migrants; Hepatitis C; Adult; Male; Prevalence; Cross-Sectional Studies; Middle Aged; Hepacivirus; Hepatitis B virus; Young Adult; COVID-19; Adolescent; Hepatitis B Surface Antigens; Hepatitis C Antibodies
PubMed: 38760415
DOI: 10.1038/s41598-024-61725-9 -
Journal of the International AIDS... May 2024
Topics: Humans; HIV Infections; HIV Antibodies; Antibodies, Neutralizing; Broadly Neutralizing Antibodies; AIDS Vaccines; HIV-1
PubMed: 38757844
DOI: 10.1002/jia2.26257 -
Virologie (Montrouge, France) May 2024Antibodies, and notably immunoglobulins A (IgA), are paramount in mucosal tissues as protective immune effectors against invading pathogens and immunomodulators of the...
Antibodies, and notably immunoglobulins A (IgA), are paramount in mucosal tissues as protective immune effectors against invading pathogens and immunomodulators of the microbiota. Upon human immunodeficiency virus type 1 (HIV-1) infection, systemic and mucosal IgA antibody responses are triggered. While naturally produced serum HIV-1 envelope protein-specific IgA are quantitatively and qualitatively weaker than their IgG counterparts, they also possess antiviral properties including neutralization and Fc-dependent functions. IgA neutralizers can block HIV-1 mucosal transmission in animal models, indicating that their elicitation by vaccination would be an important component for preventing infection. Moreover, the first genuine IgA broadly HIV-1 neutralizing antibodies (bNAbs) were recently identified in certain individuals living with HIV-1. Vaccine-based induction of IgA bNAbs potentially protective at the mucosal level is therefore conceivable. Hence, research efforts must therefore be undertaken to better understand their development and functions. In this review, we present the general functions of IgA in homeostasis and antimicrobial immunity and discuss their involvement in the antibody responses against HIV-1.
PubMed: 38757520
DOI: 10.1684/vir.2024.1049 -
Cureus Apr 2024Syphilis, caused by , remains a global health challenge, with a significant burden of new cases annually. The disease disproportionately affects men who have sex with...
Syphilis, caused by , remains a global health challenge, with a significant burden of new cases annually. The disease disproportionately affects men who have sex with men (MSMs) and endemic, low-income regions. While secondary syphilis typically manifests with a polymorphic rash, individuals with human immunodeficiency virus (HIV) coinfection may present with varied signs and symptoms. Here, we report a case of a 21-year-old male student with painful target lesions on his genitalia, deviating from the typical syphilis presentation. He was found to have concurrent molluscum contagiosum and HIV-1 infection. Serologic testing confirmed syphilis and anti-HIV-1 antibodies. Prompt initiation of antiretroviral therapy and benzathine penicillin G led to symptom resolution. This case highlights the importance of recognizing atypical painful target lesions as a potential manifestation of syphilis, especially in patients with HIV coinfection, to ensure timely diagnosis and treatment.
PubMed: 38756307
DOI: 10.7759/cureus.58382 -
PloS One 2024Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus...
BACKGROUND
Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus (HIV). The burden of hepatitis among HIV-positive individuals has not been studied in the Afar region. Therefore, this study aimed to determine the prevalence of HBV and HCV coinfection and associated factors among HIV-positive patients in Afar Regional State, northeast Ethiopia.
METHODS
A cross-sectional study was conducted on 477 HIV-positive patients between February 2019 and May 2019. A structured and pretested questionnaire was used to collect socio-demographic data and associated factors. Five milliliters of blood was collected, and Hepatitis B surface antigen (HBsAg) and HCV antibodies were detected using rapid test kits. Positive samples were confirmed using enzyme-linked immunosorbent assay (ELISA). Binary and multivariable logistic regression analyses were performed to identify associated factors. Statistical significance was set at P <0.05.
RESULTS
Among the 477 study participants, 320/477(67.1%) of them were females and 157(32.9%) males. The overall prevalence of HIV-HBV and HIV-HCV coinfection was 25(5.2%) and 7(1.5%), respectively. Multi-sexual practice was significantly associated with HIV-HBV coinfection (AOR = 5.3; 95% CI: 1.2-24.4, P = 0.032).
CONCLUSION
The prevalence of both HIV-HBV and HIV-HCV coinfection was intermediate. Multi-sexual practice was significantly associated with HIV-HBV coinfection. Screening of all HIV-positive patients for HBV and HCV and health education regarding the transmission modes should be considered.
Topics: Humans; Ethiopia; Female; Male; Adult; Hepatitis B; Coinfection; Hepatitis C; HIV Infections; Cross-Sectional Studies; Middle Aged; Prevalence; Young Adult; Adolescent; Hepatitis B Surface Antigens; Hepacivirus; Risk Factors; Hepatitis B virus
PubMed: 38753600
DOI: 10.1371/journal.pone.0302453 -
Research Square Apr 2024There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native...
There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native envelope (Env) glycoprotein structure. Recently, a novel triple tandem trimer (TTT) platform has been used to generate a plasmid encoding Env immunogen (pBG505-TTT) that expresses only as trimers, making it more suitable for nucleic acid vaccines. We have previously demonstrated that adenosine deaminase-1 (ADA-1) is critical to the T follicular helper (TFH) function and improves vaccine immune responses . In this study, we demonstrate that co-delivery of plasmid-encoded adenosine deaminase 1 (pADA) with pBG505-TTT enhances the magnitude, durability, isotype switching and functionality of HIV-specific antibodies in a dose-sparing manner. Co-delivery of the molecular immune modulator ADA-1 also enhances HIV-specific T cell polyfunctionality, activation, and degranulation as well as memory B cell responses. These data demonstrate that pADA enhances HIV-specific cellular and humoral immunity, making ADA-1 a promising immune modulator for HIV-targeting vaccines.
PubMed: 38746176
DOI: 10.21203/rs.3.rs-4139764/v1 -
PloS One 2024Persons who inject drugs (PWID) may be unengaged with healthcare services and face an elevated risk of severe morbidity and mortality associated with COVID-19 due to...
BACKGROUND
Persons who inject drugs (PWID) may be unengaged with healthcare services and face an elevated risk of severe morbidity and mortality associated with COVID-19 due to chronic diseases and structural inequities. However, data on COVID-19 vaccine uptake, particularly booster vaccination, among PWID are limited. We examined COVID-19 vaccine uptake and factors associated with booster vaccination among PWID in New York City (NYC).
METHODS
We recruited PWID using respondent-driven sampling from October 2021 to November 2023 in a survey that included HIV and SARS-CoV-2 antibodies testing. The questionnaire included demographics, COVID-19 vaccination and attitudes, and drug use behaviors.
RESULTS
Of 436 PWID, 80% received at least one COVID-19 vaccine dose. Among individuals who received at least one COVID-19 vaccine dose, 95% were fully vaccinated. After excluding participants recruited before booster authorization for general adults started in NYC, and those who had never received an initial vaccination, 41% reported having received a COVID-19 booster vaccine dose. COVID-19 booster vaccination was significantly associated with having a high school diploma or GED (adjusted odds ratio (aOR) 1.93; 95% confidence interval (CI) 1.09, 3.48), ever received the hepatitis A/B vaccine (aOR 2.23; 95% CI 1.27, 3.96), main drug use other than heroin/speedball, fentanyl and stimulants (aOR 14.4; 95% CI 2.32, 280), number of non-fatal overdoses (aOR 0.35; 95% CI 0.16, 0.70), and mean vaccination attitude score (aOR 0.94; 95% CI 0.89, 0.98).
CONCLUSIONS
We found a suboptimal level of COVID-19 booster vaccination among PWID, which was consistent with the rates observed in the general population in NYC and the U.S. Community-based interventions are needed to improve COVID-19 booster vaccination access and uptake among PWID. Attitudes towards vaccination were significant predictors of both primary and booster vaccination uptake. Outreach efforts focusing on improving attitudes towards vaccination and educational programs are essential for reducing hesitancy and increasing booster vaccination uptake among PWID.
Topics: Humans; New York City; Male; COVID-19 Vaccines; Female; Adult; COVID-19; Immunization, Secondary; Substance Abuse, Intravenous; Middle Aged; Vaccination; SARS-CoV-2; Surveys and Questionnaires; Young Adult; Drug Users
PubMed: 38743729
DOI: 10.1371/journal.pone.0303394 -
Frontiers in Immunology 2024Cytotoxic T lymphocyte (CTL) motility is an important feature of effective CTL responses and is impaired when CTLs become exhausted, e.g. during chronic retroviral...
Cytotoxic T lymphocyte (CTL) motility is an important feature of effective CTL responses and is impaired when CTLs become exhausted, e.g. during chronic retroviral infections. A prominent T cell exhaustion marker is programmed cell death protein 1 (PD-1) and antibodies against the interaction of PD-1 and PD-ligand 1 (PD-L1) are known to improve CTL functions. However, antibody blockade affects all PD-1/PD-L1-expressing cell types, thus, the observed effects cannot be attributed selectively to CTLs. To overcome this problem, we performed CRISPR/Cas9 based knockout of the PD-1 coding gene in naïve Friend Retrovirus (FV)-specific CTLs. We transferred 1,000 of these cells into mice where they proliferated upon FV-infection. Using intravital two-photon microscopy we visualized CTL motility in the bone marrow and evaluated cytotoxic molecule expression by flow cytometry. Knockout of improved the CTL motility at 14 days post infection and enhanced the expression of cytotoxicity markers. Our data show the potential of genetic tuning of naive antiviral CTLs and might be relevant for future designs of improved T cell-mediated therapies.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Cell Movement; CRISPR-Cas Systems; Cytotoxicity, Immunologic; Friend murine leukemia virus; Gene Knockout Techniques; Mice, Inbred C57BL; Mice, Knockout; Programmed Cell Death 1 Receptor; Retroviridae Infections; T-Lymphocytes, Cytotoxic
PubMed: 38742109
DOI: 10.3389/fimmu.2024.1338218