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Trials Dec 2021HIV is one of the greatest public health challenges in South Africa. Potential HIV vaccines and antibodies are thought to be cost-effective biomedical HIV prevention...
BACKGROUND
HIV is one of the greatest public health challenges in South Africa. Potential HIV vaccines and antibodies are thought to be cost-effective biomedical HIV prevention methods and are currently under investigation in phase I, II, and III trials. Consequently, current and future clinical trials need to ensure sufficient recruitment and retention. To achieve this goal, clinical trial staff need to understand the socio-demographic and behavioural characteristics of people volunteering to screen for these trials and their reasons for volunteering.
METHODS
We conducted a secondary analysis of participant screening data across five vaccine and monoclonal antibody trials at four sites in KwaZulu-Natal, South Africa. Our study reviewed the demographic, behavioural, motivational, and health-related data from the case report forms and screening questionnaires. Descriptive statistics, chi-squared, and one-way ANOVA tests were used to analyse participants' characteristics and motivation to participate in HIV vaccine and monoclonal antibody trials. Analyses were conducted using R version 3.5.2.
RESULTS
Screening data from 1934 participants, including 79.2% of women, were obtained across all five trials (1034 enrolled, 900 screened out/declined). Screened participants predominately self-identified as black, heterosexual, cisgender women or men, many with lower educational backgrounds (43.9% did not complete secondary/high school), and several self-reported HIV-risk behaviours among themselves and their partners. 10.8% of the screened participants were living with HIV. Avoiding HIV risk was the main motivation to participate in clinical trials, followed by altruistic reasons such as a desire to help the community or helping to find a vaccine.
DISCUSSION
The current recruitment approach of these trials attracts heterosexual participants who seek to reduce HIV risk and support their community. Hence, the data suggest the need for and potential acceptance of continued ongoing HIV prevention efforts. Current trials attract participants with lower educational levels, which may be driven by the site locations, current community mobilisation strategies and research site opening hours. The sites could consider more flexible working hours to accommodate working participants and find ways to connect participants to educational support and opportunities to upgrade education levels for the current clientele.
TRIAL REGISTRATION
HVTN 100: A Safety and Immune Response Study of 2 Experimental HIV Vaccines, NCT02404311 . Registered on March 17, 2015. HVTN 111: Safety and Immune Response to a Clade C DNA HIV Vaccine, NCT02997969. Registered on December 16, 2016. HVTN 108: Evaluating the Safety and Immunogenicity of HIV Clade C DNA Vaccine and MF59- or AS01B-Adjuvanted Clade C Env Protein Vaccines in Various Combinations in Healthy, HIV-Uninfected Adults, NCT02915016. Registered on September 22, 2016. HVTN 702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa, NCT02968849. Registered on November 1, 2016. HVTN 703/HPTN 081: Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women, NCT02568215 . Registered on October 1, 2015.
Topics: AIDS Vaccines; Adult; Antibodies, Monoclonal; Female; HIV Infections; Humans; Male; Motivation; South Africa
PubMed: 34895272
DOI: 10.1186/s13063-021-05792-7 -
AIDS (London, England) Jan 2023Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Our objective was to compare COVID-19 vaccine...
OBJECTIVES
Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Our objective was to compare COVID-19 vaccine immunogenicity in PWH to HIV-negative individuals.
DESIGN
In a Canadian multi-center prospective, observational cohort of PWH receiving at least two COVID-19 vaccinations, we measured vaccine-induced immunity at 3 and 6 months post 2nd and 1-month post 3rd doses.
METHODS
The primary outcome was the percentage of PWH mounting vaccine-induced immunity [co-positivity for anti-IgG against SARS-CoV2 Spike(S) and receptor-binding domain proteins] 6 months post 2nd dose. Univariable and multivariable logistic regressions were used to compare COVID-19-specific immune responses between groups and within subgroups.
RESULTS
Data from 294 PWH and 267 controls were analyzed. Immunogenicity was achieved in over 90% at each time point in both groups. The proportions of participants achieving comparable anti-receptor-binding domain levels were similar between the group at each time point. Anti-S IgG levels were similar by group at month 3 post 2nd dose and 1-month post 3rd dose. A lower proportion of PWH vs. controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose [92% vs. 99%; odds ratio: 0.14 (95% confidence interval: 0.03, 0.80; P = 0.027)]. In multivariable analyses, neither age, immune non-response, multimorbidity, sex, vaccine type, or timing between doses were associated with reduced IgG response.
CONCLUSION
Vaccine-induced IgG was elicited in the vast majority of PWH and was overall similar between groups. A slightly lower proportion of PWH vs. controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose demonstrating the importance of timely boosting in this population.
Topics: Humans; COVID-19 Vaccines; Immunogenicity, Vaccine; Prospective Studies; RNA, Viral; COVID-19; Canada; SARS-CoV-2; HIV Infections; Antibodies; AIDS Vaccines
PubMed: 36476452
DOI: 10.1097/QAD.0000000000003429 -
Frontiers in Immunology 2021CXCL13 signals through the G protein-coupled chemokine receptor CXCR5 to drive development of secondary lymphoid tissue as well as B cell and Tfh cell trafficking to... (Review)
Review
CXCL13 signals through the G protein-coupled chemokine receptor CXCR5 to drive development of secondary lymphoid tissue as well as B cell and Tfh cell trafficking to germinal centers (GC), which leads to the differentiation of B cells to plasma cells and memory B cells. CXCL13 has been proposed as a general plasma biomarker for GC activities. In HIV-1 infected individuals, plasma CXCL13 levels have been associated with the rate of disease progression to AIDS. Moreover, CXCL13 production has been reported to be increased in HIV-1-infected lymph nodes, which may drive increased downregulation of CXCR5. In this review, we address the role of CXCL13 in HIV-1 infected individuals with regard to GC formation, generation of broadly neutralizing antibodies after infection and vaccination, and AIDS-related B cell lymphoma.
Topics: AIDS Vaccines; Antibody Formation; Broadly Neutralizing Antibodies; Chemokine CXCL13; HIV Antibodies; HIV Infections; HIV-1; Humans
PubMed: 33732259
DOI: 10.3389/fimmu.2021.638872 -
Archives of Virology May 2021In 2006 we discovered a new type of mucosal vaccine against simian immunodeficiency virus (SIV) in Chinese macaques. Here, we review 15 years of our published work on... (Review)
Review
In 2006 we discovered a new type of mucosal vaccine against simian immunodeficiency virus (SIV) in Chinese macaques. Here, we review 15 years of our published work on this vaccine, which consists of inactivated SIVmac239 particles adjuvanted with Bacillus Calmette-Guérin, Lactobacillus plantarum, or Lactobacillus rhamnosus. Without adjuvant, the vaccine administered by the intragastric route induced the usual SIV-specific humoral and cellular immune responses but provided no protection against intrarectal challenge with SIVmac239. In contrast, out of 24 macaques immunized with the adjuvanted vaccine and challenged intrarectally with SIVmac239 or SIVB670, 23 were sterilely protected for up to five years, while all control macaques were infected. This protection was confirmed by an independent group from the Pasteur Institute. During the past 15 years, we have identified the mechanism of action of the vaccine and discovered that the vaccinated macaques produced a previously unrecognized class of MHC-Ib/E-restricted CD8 T cells (which we refer to as tolerogenic CD8 T cells) that suppressed the activation of SIV-RNA-infected CD4 T cells and thereby inhibited the (activation-dependent) reverse transcription of the virus, which in turn prevented the establishment of SIV infection. Importantly, we discovered also that the tolerogenic CD8 T cell subset observed in vaccinated Chinese macaques could also be found in human elite controllers, a small group of HIV-infected patients in whom these tolerogenic CD8 T cells were shown to naturally suppress viral replication. Given that SIV and HIV require activated immune cells in which to replicate, the specific prevention of activation of SIV-RNA-containing CD4 T cells by a tolerogenic vaccine approach offers an exciting new avenue in HIV vaccine research.
Topics: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; HIV Infections; Humans; Macaca mulatta; Simian Immunodeficiency Virus; Virus Replication
PubMed: 33507389
DOI: 10.1007/s00705-020-04935-6 -
Cell Jun 2020The SARS-CoV-2 pandemic that causes COVID-19 respiratory syndrome has caused global public health and economic crises, necessitating rapid development of vaccines and... (Review)
Review
The SARS-CoV-2 pandemic that causes COVID-19 respiratory syndrome has caused global public health and economic crises, necessitating rapid development of vaccines and therapeutic countermeasures. The world-wide response to the COVID-19 pandemic has been unprecedented with government, academic, and private partnerships working together to rapidly develop vaccine and antibody countermeasures. Many of the technologies being used are derived from prior government-academic partnerships for response to other emerging infections.
Topics: AIDS Vaccines; Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Betacoronavirus; COVID-19; COVID-19 Vaccines; Coronavirus Infections; Humans; Intersectoral Collaboration; Pandemics; Pneumonia, Viral; SARS-CoV-2; Viral Vaccines; COVID-19 Drug Treatment
PubMed: 32492407
DOI: 10.1016/j.cell.2020.05.041 -
Science (New York, N.Y.) Dec 2019Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of...
Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.
Topics: AIDS Vaccines; Adoptive Transfer; Amino Acid Sequence; Animals; B-Lymphocytes; Broadly Neutralizing Antibodies; Complementarity Determining Regions; Directed Molecular Evolution; Disease Models, Animal; HEK293 Cells; HIV Antibodies; Humans; Immunogenicity, Vaccine; Mice; Mice, Knockout; Precursor Cells, B-Lymphoid; env Gene Products, Human Immunodeficiency Virus
PubMed: 31672916
DOI: 10.1126/science.aax4380 -
Expert Review of Vaccines 2023Over the last four decades, human immunodeficiency virus type 1 (HIV-1) infection has been a major public health concern. It is acknowledged that an effective vaccine...
INTRODUCTION
Over the last four decades, human immunodeficiency virus type 1 (HIV-1) infection has been a major public health concern. It is acknowledged that an effective vaccine remains the best hope for eliminating the HIV-1 pandemic. The prophylaxis of HIV-1 infection remains a central theme because of the absence of an available HIV-1 vaccine. The inability of conventional delivery strategies to induce potent immunity is a crucial task to overcome and ultimately lead to a major obstacle in HIV-1 vaccine research.
AREAS COVERED
The literature search was conducted in the following databases: PubMed, Web of Science, and Embase. Nano-platforms-based vaccines have proven prophylaxis in various diseases for effectively activating the immune system. Nano-vaccines, including non-viral and viral vectored nano-vaccines, are in a position to improve the effectiveness of HIV-1 antigen delivery and enhance the innate and adaptive immune responses against HIV-1. Compared to traditional vaccination strategies, genetic immunization can elicit a long-term immune response to provide protective immunity for HIV-1 prevention.
EXPERT OPINION
Research progress on nano-vaccines for gene delivery against HIV-1 was discussed. Vaccine strategies based on nano-platforms that are being applied to stimulate effective HIV-1-specific cellular and humoral immune responses were particularly emphasized.
Topics: Humans; HIV-1; HIV Infections; Immunity, Humoral; Viral Vaccines; Vaccination; AIDS Vaccines
PubMed: 36945780
DOI: 10.1080/14760584.2023.2193266 -
Frontiers in Immunology 2022
Topics: AIDS Vaccines; HIV Infections; HIV-1; Humans; T-Lymphocytes
PubMed: 35572584
DOI: 10.3389/fimmu.2022.905836 -
Current Opinion in HIV and AIDS Nov 2023Explore whether immunization with germline-targeting Env immunogens during ART, followed by ATI, leads to the identification of viral envelope glycoproteins (Envs) that... (Review)
Review
PURPOSE OF REVIEW
Explore whether immunization with germline-targeting Env immunogens during ART, followed by ATI, leads to the identification of viral envelope glycoproteins (Envs) that promote and guide the full maturation of broadly neutralizing antibody responses.
RECENT FINDINGS
The HIV-1 envelope glycoprotein (Env) does not efficiently engage the germline precursors of broadly neutralizing antibodies (bnAbs). However, Env-derived proteins specifically designed to precisely do that, have been recently developed. These 'germline-targeting' Env immunogens activate naïve B cells that express the germline precursors of bnAbs but by themselves cannot guide their maturation towards their broadly neutralizing forms. This requires sequential immunizations with heterologous sets of Envs. These 'booster' Envs are currently unknown.
SUMMARY
Combining germline-targeting Env immunization approaches during ART with ATI could lead to the identification of natural Envs that are responsible for the maturation of broadly neutralizing antibody responses during infection. Such Envs could then serve as booster immunogens to guide the maturation of glBCRs that have become activated by germline-targeting immunogens in uninfected subjects.
Topics: Humans; HIV Infections; HIV Antibodies; Broadly Neutralizing Antibodies; HIV-1; Antibodies, Neutralizing; env Gene Products, Human Immunodeficiency Virus; Immunization; Vaccines; AIDS Vaccines
PubMed: 37712859
DOI: 10.1097/COH.0000000000000817 -
Journal of the Pediatric Infectious... May 2022Our study explores the understanding of vaccine-induced seropositivity (VISP) and its potential impact on US adolescents' and caregivers' willingness to participate in...
Our study explores the understanding of vaccine-induced seropositivity (VISP) and its potential impact on US adolescents' and caregivers' willingness to participate in adolescent HIV vaccine clinical trials. Findings from in-depth interviews suggest that addressing concerns about VISP will be essential for future pediatric HIV vaccine trials in the United States.
Topics: AIDS Vaccines; Adolescent; Child; HIV Infections; Health Knowledge, Attitudes, Practice; Humans; United States
PubMed: 35139223
DOI: 10.1093/jpids/piac001