Human Immunodeficiency Virus Vaccine Research Articles

Perceptions and Acceptance of a Prophylactic Vaccine for Human Immunodeficiency Virus (HIV): A Qualitative Study.

Despite advances in human immunodeficiency virus (HIV) prevention methods, such as the advent of pre-exposure prophylaxis (PrEP), the number of people with newly acquired HIV remains high, particularly in at-risk groups. A prophylactic HIV vaccine could contribute to reduced disease prevalence and future transmission and address limitations of existing options, such as suboptimal long-term adherence to PrEPs. This qualitative study aimed to capture perceptions towards and acceptance of prophylactic HIV vaccination in three adult populations in the United States: the general population, 'at-risk' individuals (e.g. men who have sex with men, transgender individuals, gender-nonconforming individuals, and individuals in a sexual relationship with a person living with HIV), and parents/caregivers of children aged 9-17years. Interviews were conducted with 55 participants to explore key drivers and barriers to HIV vaccine uptake, and a conceptual model was developed. The sample was diverse; participants were 51% female, aged 20-57 years (mean 37years), 33% with high school diploma as highest education level, and identified as White (42%), Black or African American (35%), of Hispanic, Latino, or Spanish origin (22%), or other races/ethnicities (8%) [groupings are not mutually exclusive]. Perceptions were influenced by individual, interpersonal, community, institutional, and structural factors. Overall, 98% of participants thought vaccination would be beneficial in preventing HIV. Key considerations/barriers included perceived susceptibility, i.e. whether participants felt there was a risk of contracting HIV (discussed by 90%); the clinical profile of the vaccine (e.g. the adverse effect profile [98%], and vaccine efficacy [85%], cost [73%] and administration schedule [88%]); and concerns around potential vaccine-induced seropositivity (VISP; 62%). Stigma was not found to be an important barrier, with a general view that vaccination status was personal. Participants in the 'at-risk' group were the most likely to accept an HIV vaccine (70%). Unique concerns in the subgroups included how a potential vaccine's clinical profile compared with PrEP, voiced by those receiving/considering PrEP, and considerations of children's views on the topic, voiced by parents/caregivers. Understanding these factors could help develop HIV vaccine research strategies and contribute toward public health messaging to support future HIV vaccination programs.

A J Paramyxovirus-vectored HIV vaccine induces humoral and cellular responses in mice

Human immunodeficiency virus (HIV) infects and depletes CD4+ T-cells, resulting in Acquired Immunodeficiency Syndrome (AIDS) and death. Despite numerous clinical trials, there is no licensed HIV vaccine. The HIV envelope glycoprotein (env) is a major target for vaccine development, especially for the development of antibody-mediated protection. In this study, we used J paramyxovirus (JPV) as a viral vector to express HIV-env. We replaced the JPV small hydrophobic (SH) gene with HIV-env (rJPV-env). Intranasal rJPV-env immunization induced anti-HIV-gp120 IgG antibodies in mice. Furthermore, we examined the immunogenicity of homologous and heterologous prime/boost regimens with rJPV-env, parainfluenza virus 5 (rPIV5)-vectored HIV-env, and HIV-Gag-Env virus-like particles (VLPs). The rJPV-env/rPIV5-env heterologous prime/boost regimen induced the strongest humoral and cellular responses. Introducing a third dose of immunization, mice that received a viral-vectored prime had high levels of HIV-env-specific cellular responses, with group rJPV-env/rPIV5-env/VLP having the highest. Together, this work indicates that a heterologous combination of viral-vectored HIV-env vaccines and a HIV-Gag-Env VLP induces high levels of humoral and cellular responses against HIV in mice.

Impact of Recombinant VSV-HIV Prime, DNA-Boost Vaccine Candidates on Immunogenicity and Viremia on SHIV-Infected Rhesus Macaques.

Currently, no effective vaccine to prevent human immunodeficiency virus (HIV) infection is available, and various platforms are being examined. The vesicular stomatitis virus (VSV) vaccine vehicle can induce robust humoral and cell-mediated immune responses, making it a suitable candidate for the development of an HIV vaccine. Here, we analyze the protective immunological impacts of recombinant VSV vaccine vectors that express chimeric HIV Envelope proteins (Env) in rhesus macaques. To improve the immunogenicity of these VSV-HIV Env vaccine candidates, we generated chimeric Envs containing the transmembrane and cytoplasmic tail of the simian immunodeficiency virus (SIV), which increases surface Env on the particle. Additionally, the Ebola virus glycoprotein was added to the VSV-HIV vaccine particles to divert tropism from CD4 T cells and enhance their replications both in vitro and in vivo. Animals were boosted with DNA constructs that encoded matching antigens. Vaccinated animals developed non-neutralizing antibody responses against both the HIV Env and the Ebola virus glycoprotein (EBOV GP) as well as systemic memory T-cell activation. However, these responses were not associated with observable protection against simian-HIV (SHIV) infection following repeated high-dose intra-rectal SHIV SF162p3 challenges.

Comprehension of informed consent and voluntary participation in registration cohorts for phase IIb HIV vaccine trial in Dar Es Salaam, Tanzania: a qualitative descriptive study

BackgroundInformed consent as stipulated in regulatory human research guidelines requires volunteers to be well-informed about what will happen to them in a trial. However, researchers may be faced with the challenge of how to ensure that a volunteer agreeing to take part in a clinical trial is truly informed. This study aimed to find out volunteers’ comprehension of informed consent and voluntary participation in Human Immunodeficiency Virus (HIV) clinical trials during the registration cohort.MethodsWe conducted a qualitative study among volunteers who were enrolled in the registration cohort of HIV clinical trials in Dar es Salaam, Tanzania. A purposive sampling strategy was used to obtain twenty study participants. The data were collected between June and September 2020 using a semi-structured interview guide. In-depth interviews were used to collect the data to obtain deep insights of the individual study participants on the comprehension of informed consent and participation in the clinical trial. A thematic analysis approach was used to analyze the data. Themes and subthemes were supported by the quotes from the participants.ResultsVolunteers described comprehension of informed consent from different perspectives. They reported that various components of the informed consent such as study procedure, confidentiality, risk and benefits were grasped during engagement meetings. Furthermore, the volunteers’ decision to participate in the registration cohort was voluntary. However, trial aspects such as health insurance, free condoms, and medical checkups could have indirectly influenced their reluctance to withdraw from the study.ConclusionEngagement meetings may increase the comprehension of informed consent among potential participants for HIV clinical trials. However, trial incentives may influence participation, and thus future research should focus on the challenges of giving incentives in the study. This will ensure comprehension and voluntary participation in the context of HIV clinical trials.

Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combating the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

Application of Memory Natural Killer Cells in HIV Vaccine

Human immunodeficiency virus (HIV) is a formidable infection targeting the intricate defense mechanisms of the human body, primarily focusing its assault on the vital white blood cells known as CD4 cells. HIV impairs these CD4 cells, reducing resistance to opportunistic infections. In 2022, 630,000 people died from HIV-related causes globally due to the lack of preventative vaccines and effective treatment. The pursuit of an effective HIV vaccine remains a critical endeavor in global health, necessitating innovative strategies that can elicit robust and durable immune responses. Natural killer (NK) cells, renowned for their swift and inherent cytotoxic prowess, constitute a critical element of innate immunity, typically thought to be deficient in memory abilities. Fascinatingly, NK cells have now become the focal point of scientific research due to emerging evidence suggesting the presence of memory-like characteristics within their functional repertoire. Through a comprehensive exploration of NK cell subpopulations and the strategic application of cytokines or other stimuli to induce the development of memory-generating NK cell subpopulations, the potential for enhancing the efficacy of HIV vaccines emerges. This approach holds promise in bolstering the creation of adaptive immunity and advancing the quest for effective HIV immunization strategies. The study offers valuable insights into the potential of NK memory cells as a viable component of future HIV vaccine regimens, suggesting avenues for further research and development in the quest to mitigate the global burden of HIV.

Major HIV vaccine candidates

Introduction and objective: Human immunodeficiency virus (HIV) is a virus, which is responsible for an acquired immunodeficiency syndrome (AIDS). This pathogen is widespread worldwide causing a pandemic that has been going on for decades. Researches around the world are trying to end this situation and it seems that the greatest hope lies in finding an effective vaccine. It is important due to the fact that AIDS and its consequences are responsible even nowadays for death of many people infected around the world. The aim of this study was to provide the most important information about major HIV vaccine trials and efficacy of vaccine candidates.
 Materials and methods: For the purposes of writing this article, the available literature was reviewed. The database of medical publications – Pubmed datebase and other publicaly available books, database and online sites was searched, with the use of keywords such as HIV, HIV vaccine, HIV epidemiology.
 State of knowledge: According to review studies HIV vaccine trials has been going for 4 decades. Over 250 trials has been conducted since then, but unfortunately, none of them resulted in effective vaccine. The difficulties of this task are mainly connected with the nature of HIV virus. To date, one study has shown some effectiveness, but not enough to claim success. Other studies are ongoing around the world and more are planned.
 Conclusions: Developing an effective HIV vaccine is the clue to solving the problem, which is new HIV infections. Further researches, further research funding and international cooperation are needed to end this pandemic.

Safety and Immunogenicity of the ID93 +GLA-SE Tuberculosis Vaccine in BCG-Vaccinated Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

This randomized, double-blind, placebo-controlled, phase 2a trial was conducted to evaluate the safety and immunogenicity of the ID93+ glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) vaccine in human immunodeficiency virus (HIV)-negative, previously Bacillus Calmette-Guérin (BCG)-vaccinated, and QuantiFERON-TB-negative healthy adults in South Korea. Adults (n = 107) with no signs or symptoms of tuberculosis were randomly assigned to receive three intramuscular injections of 2μg ID93 + 5μg GLA-SE, 10μg ID93 + 5μg GLA-SE, or 0.9% normal saline placebo on days 0, 28, and 56. For safety assessment, data on solicited adverse events (AEs), unsolicited AEs, serious AEs (SAEs), and special interest AEs were collected. Antigen-specific antibody responses were measured using serum enzyme-linked immunosorbent assay. T-cell immune responses were measured using enzyme-linked immunospot and intracellular cytokine staining. No SAEs, deaths, or AEs leading to treatment discontinuation were found. The solicited local and systemic AEs observed were consistent with those previously reported. Compared with adults administered with the placebo, those administered with three intramuscular vaccine injections exhibited significantly higher antigen-specific antibody levels and Type 1T-helper cellular immune responses. The ID93 + GLA-SE vaccine induced antigen-specific cellular and humoral immune responses, with an acceptable safety profile in previously healthy, BCG-vaccinated, Mycobacteriumtuberculosis-uninfected adult healthcare workers. This clinical trial was retrospectively registered on 16 January 2019 at Clinicaltrials.gov (NCT03806686).

Improvement of B Cell Responses by an HIV-1 Amphiphilic Polymer Nanovaccine.

The human immunodeficiency virus (HIV) has infected over 84 million people since its discovery and is a huge threat to human health. While an HIV vaccine is urgently needed to curb this devastating pandemic, it has been notoriously difficult to develop, partly due to the extraordinary high level of genetic variation of HIV. We designed a new HIV-1 envelope glycoprotein nanoparticle (Env/NP) vaccine using amphiphilic polymers. The Env/NP vaccine induced more potent and broader neutralizing activities against multiple HIV-1 subtypes. Moreover, it elicits similar neutralizing antibody responses after the storage at -80 °C, 4 °C or room temperature post lyophilization. These results demonstrate that the new Env/NP vaccine not only improves the HIV vaccine immune responses but also is stable under different storage conditions. This new nanovaccine approach can readily apply to other protein-based vaccines.

Purification of recombinant vesicular stomatitis virus-based HIV vaccine candidate.

In this work, laboratory- and large-scale methods were tested for purification of a human immunodeficiency virus (HIV) vaccine candidate, based on recombinant vesicular stomatitis virus (rVSV). First step of the purification, the clarification of the rVSVs produced in serum-free cell culture medium, was tested by centrifugation and filtration using different filtration media and pore sizes (0.45 to 30µm). To reduce the supernatant volume and process time, the clarified sample was concentrated by ultrafiltration either using tangential flow filtration or centrifugal-based filtration units, depending on the process scale. The final purification step at laboratory-scale, was carried out by density gradient ultracentrifugation, the recovery of which was compared with chromatographic purification at large-scale. The virus preparations were analyzed using dynamic light scattering to verify the virus size and transmission electron microscopy for purity and virus morphology. Density gradient ultracentrifugation allowed the recovery of≥80% infectious particles and reduced the contaminant DNA and host cell proteins relatively to standard ultracentrifugation pelleting using a sucrose cushion. At large-scale, weak and strong anion-exchangers were tested and compared. The best columns allowed infectious virus recoveries as high as 77% and eliminated 92% of host cell proteins.

Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay.

Immunological protection against human immunodeficiency virus-1 (HIV-1) infection is likely to require both humoral and cell-mediated immune responses, the latter involving cytotoxic CD8 T-cells. Characterisation of CD8 T-cell mediated direct anti-viral activity would provide understanding of potential correlates of immune protection and identification of critical epitopes associated with HIV-1 control. The present report describes a functional viral inhibition assay (VIA) to assess CD8 T-cell-mediated inhibition of replication of a large and diverse panel of 45 HIV-1 infectious molecular clones (IMC) engineered with a Renilla reniformis luciferase reporter gene (LucR), referred to as IMC-LucR. HIV-1 IMC replication in CD4 T-cells and CD8 T-cell mediated inhibition was characterised in both ART naive subjects living with HIV-1 covering a broad human leukocyte antigen (HLA) distribution and compared with uninfected subjects. CD4 and CD8 T-cell lines were established from subjects vaccinated with a candidate HIV-1 vaccine and provided standard positive controls for both assay quality control and facilitating training and technology transfer. The assay was successfully established across 3 clinical research centres in Kenya, Uganda and the United Kingdom and shown to be reproducible. This IMC-LucR VIA enables characterisation of functional CD8 T-cell responses providing a tool for rational T-cell immunogen design of HIV-1 vaccine candidates and evaluation of vaccine-induced T-cell responses in HIV-1 clinical trials.

The Clinic trials of Human Immunodeficiency Virus

This review paper looks for future improvement for HIV. It is obvious that HIV has become a pandemic disease and causes serious problems to human life quality, social stability and public health. However, there are still a lot people get infected by HIV and the mortality of HIV patients has decreased compared with the time that the disease was discovered. By understanding the virus structure and the mechanisms when the pathogen enters the body, humans can find ways to solve AIDS infection in these ways, from the source of the pathogen, the transmission path, and patients infected by HIV. Second, by analyzing two successful cases of HIV cured patients and the failure cases, humans find out that not everybody is suitable for the same treatments as the two successful cased did. Although, nowadays, scientists are working on HIV vaccines, the process is very slow as there are still a lot of mysteries in human immunodeficiency virus and HIV vaccines. Few types of vaccines were undergoing clinical trials. Humans still have a long way to go to overcome HIV, but as more and more attention are paid to HIV patients and the projects which are trying to overcome it, HIV patients’ life quality had improved a lot and their life cycles are prolonged.

Acceptability of and willingness to pay for human immunodeficiency virus vaccination: A systematic literature review

Context: Vaccines for the human immunodeficiency virus (HIV) have considerably improved public health in the last century. Important considerations, however, are that effective vaccination substantially depends on the acceptability of future vaccines and that monetary measurements of vaccine preference, as reflected by the willingness to pay (WTP), may help policymakers establish health capital priorities. Aims: To systematically pool data on vaccine acceptability and WTP. Methods: A systematic search was performed over five databases to identify eligible articles published from 2005 to 2020, and key terms were used in accordance with the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Two researchers independently assessed the articles, extracted relevant data, and drew numerical and descriptive summaries for result presentation via Excel. Results: Out of 31 eligible studies, 28 and 3 reported on the acceptability of and WTP for HIV vaccination, respectively. Acceptability levels ranged from 2.94% to 93.10%, with the average being 60.16%, and WTP values fell between US$108 and US$671. The most prevalent themes were the characteristics of HIV vaccines (safety/side effects, efficacy, duration of protection, vaccine-induced seropositivity). Conclusions: Overall, the review uncovered a lack of standardized, universal, and acceptable scales for determining acceptability and WTP. The evaluation provided a comprehensive and systematic summary of these matters along with useful information for policymakers on maximizing public health under limited resources.

Identification and molecular characterization of simian endogenous retrovirus in Macaca fascicularis and Macaca nemestrina from captive breeding facilities in Bogor, Indonesia.

Background and Aim:Endogenous retroviruses (ERVs) found in all vertebrates, including non-human primates (NHPs), are known to be genetically inherited. Thus, recent studies have explored ERVs for human immunodeficiency virus vaccine development using human ERV (HERV) due to the hypervariability of exogenous retroviruses which cause conventional vaccines to be ineffective. HERV was also found to be able to induce an immune response in cancer patients. This study aimed to identify and molecularly characterize ERVs from Indonesian NHPs: Macaca fascicularis and Macaca nemestrina. Then, we described the phylogenetic relationship of these isolates with those of the simian ERVs (SERVs) characterized in other species and countries.Materials and Methods:First, 5 mL of whole blood samples was taken from 131 long-tailed macaques and 58 pig-tailed macaques in captive breeding facilities at Bogor, Indonesia, for DNA extraction. Next, the DNA samples were screened using the SYBR Green real-time polymerase chain reaction (PCR) technique with specific primers for env (simian retroviruses [SRV]1-5 7585U19 and SRV1-5 7695L21). Positive SERV results were those with cycle threshold (CT) values < 24 (CT < 24) and melting temperature (TM) ranges of 80°C–82°C. Then, whole-genome nucleotide sequences from two pig-tailed macaques samples detected as positive SERV were generated using a nucleic acid sequencing technique which utilized the walking primer method. Subsequently, the sequences were analyzed using bioinformatics programs, such as 4Peaks, Clustal Omega, and BLAST (NCBI). Subsequently, a phylogenetic tree was constructed using the neighbor-joining method in MEGA X.Results:SYBR Green real-time PCR amplification results indicated that SERV (Mn B1 and Mn B140910)-positive samples had CT values of 22.37–22.54 and TM of 82°C. Moreover, whole-genome sequences resulted in 7991 nucleotide sequences, comprising long terminal repeat, gag, pro, pol, and env genes identical between the sequenced samples. Furthermore, the phylogenetic tree results indicated that both samples from M. nemestrina had 99%–100% nucleotide identities to the Mn 92227 sample identified at the National Primate Center University of Washington (NaPRC UW) which was imported from Indonesia in 1998, confirmed as a novel SERV strain. The phylogenetic tree results also indicated that although SERV whole-genome nucleotide and env amino acid sequences were clustered with SRV-2 (identity values of 82% and 79%, respectively), they had a 99%–100% nucleotide identity to Mn 92227. Meanwhile, the gag, pro, and pol amino acids were clustered with SRV-1, SRV-3, SRV-4, SRV-5, SRV-8, and SERV/1997, with 82% and 88% identity values.Conclusion:Based on the SYBR Green real-time PCR profiles generated, similarities with Mn 92227 were observed. Subsequent phylogenetic analysis confirmed that both samples (Mn B1 and Mn B140919) from pig-tailed macaques in the country of origin were novel SERV strains at NaPRC UW. Therefore, it could be used in biomedical research on ERVs.

MRNA-based vaccine technology for HIV.

Human immunodeficiency virus (HIV) poses a major health problem around the globe, resulting in hundred-thousands of deaths from AIDS and over a million new infections annually. Although the standard treatment of HIV infection, antiretroviral therapy, has proven effective in preventing HIV transmission, it is unsuitable for worldwide use due to its substantial costs and frequent adverse effects. Besides promoting HIV/AIDS awareness through education, there is hardly an alternative for inhibiting the spread of the disease. One promising approach is the development of an HIV vaccine. Unfortunately, the high variability of envelope proteins from HIV subtypes, their frequency of mutation and the lack of fully understanding the mechanisms of protection against the virus constitute an obstacle for vaccine development. Efforts for developing successful anti-HIV vaccines have been underway for decades now, with little success. Lately, significant progress has been made in adopting the novel mRNA vaccine approach as an anti-HIV strategy. mRNA vaccines received a great thrust during the COVID-19 pandemic. Now, several mRNA-based HIV vaccines are undergoing clinical trials to evaluate their safety and efficacy. This review offers an overview of the pathogenesis and treatment of HIV / AIDS, previous efforts of HIV vaccine development and introduces mRNA vaccines as a promising and potential game changing platform for HIV vaccination.

Circumventing HIV-1 immune evasion strategies: utilizing broadly neutralizing antibodies to bolster current drug treatments and develop novel vaccines

Human immunodeficiency virus (HIV) attacks the human immune system and if left untreated, causes acquired immunodeficiency syndrome (AIDS). Since its discovery, HIV has quickly become a major public health concern, infecting roughly one million people worldwide each year. HIV employs several immune evasion mechanisms including the targeting of key immune cells, integration of its genome into the host, and infection of uninfected cells through virologic synapses. Advances in antiretroviral therapy (ART) and knowledge of HIV-1 immune evasion strategies have improved our clinical understanding of its pathogenesis and informed new approaches towards developing a vaccine. The primary objective of ART treatment is to lower HIV viral loads and slow the progression to AIDS though the high mutation rate associated with retroviruses facilitates the creation of drug resistant strains. While this presents a challenge to the development of novel drug therapies, there have been several recent breakthroughs using the infusion of broadly neutralizing antibodies (bnAbs) to support ART regimens. Unfortunately, bnAbs are rare and HIV patients have weakened natural immunity to the virus, which complicates vaccine development. Recently, researchers have seen encouraging concentrations of HIV-specific antibodies using a rubella-based live attenuated vaccine in non-human primates though the transition from animal models to human clinical trials has been traditionally cumbersome. Given more recent advancements in our understanding of viral shell disorder, perhaps it is time to consider why the development of an HIV vaccine has been so problematic and to devise new strategies to combat this disease moving forward.

Immunopotentiation by linking Hsp70 T-cell epitopes to Gag-Pol-Env-Nef-Rev multiepitope construct and increased IFN-gamma secretion in infected lymphocytes

Therapeutic human immunodeficiency virus (HIV) vaccines can boost the anti-HIV host immunity to control viral replication and eliminate viral reservoirs in the absence of anti-retroviral therapy. In this study, two computationally designed multiepitope Gag-Pol-Env-Nef-Rev and Hsp70-Gag-Pol-Env-Nef-Rev constructs harboring immunogenic and highly conserved HIV T cell epitopes were generated in E. coli as polypeptide vaccine candidates. Furthermore, the multiepitope gag-pol-env-nef-rev and hsp70-gag-pol-env-nef-rev DNA vaccine constructs were prepared and complexed with MPG cell-penetrating peptide. The immunogenicity of the multiepitope constructs were evaluated using the homologous and heterologous prime/boost strategies in mice. Moreover, the secretion of IFN-γ was assessed in infected lymphocytes in vitro. Our data showed that the homologous polypeptide regimens could significantly induce a mixture of IgG1 and IgG2a antibody responses, activate T cells to secret IFN-γ, IL-5, IL-10, and generate Granzyme B. Moreover, IFN-γ secretion was significantly enhanced in single-cycle replicable (SCR) HIV-1 virions-infected splenocytes in these groups compared to uninfected splenocytes. The linkage of heat shock protein 70 (Hsp70) epitopes to Gag-Pol-Env-Nef-Rev polypeptide in the homologous regimen increased significantly cytokines and Granzyme B levels, and IFN-γ secretion in virions-infected splenocytes. Briefly, both designed constructs in the homologous regimens can be used as a promising vaccine candidate against HIV infection.

Distinct immune profiles of HIV-infected subjects are linked to specific lipid mediator signature.

Introduction:To date, with no prophylactic human immunodeficiency virus (HIV) vaccine available, HIV incidence rates remain undefeated. Despite full virological suppression, HIV+ individuals exhibit a higher rate of cardiovascular disorders and cancers what is attributed to the residual, persistent levels of immune activation.Methods:We have established the Virological and Immunological Monitoring (VIM) platform and forty VIM samples that included treated immunological responders (IRs) or nonresponders (INRs), viremic untreated subjects and uninfected controls, were phenotyped by flow cytometry and plasma was used to quantify proinflammatory eicosanoids and the specialized proresolving mediators by liquid chromatography tandem mass spectrometry.Results:While HIV infection profoundly altered lipid mediator (LM) profile, differences were also seen in patients on viral suppressive therapy. IRs exhibited higher levels of proresolving mediators as compared to INRs and notable differences in plasma LM were also seen in early and late treated individuals.Conclusions:This study demonstrated distortions in proinflammatory/proresolution processes in infected patients including those with controlled viremia.

Magnitude of antibiotic resistant bacterial colonization of women attending HIV clinic in Lagos, Nigeria

Opportunistic infections due microorganisms particularly bacteria have posed a threat and thus an addition burden on the management of human immunodeficiency virus (HIV) infections worldwide. The high prevalence of bacterial pathogens and the emergence of multiple drug resistance among such bacteria call for serious concern. Bacteriological examination of 320 women attending HIV clinics was carried out using standard microbiological techniques. The antimicrobial susceptibility testing was carried out by the disc diffusion technique by Bauer and CLSI. Of the 320 women, 200 (62.5%) had bacteria, 120 women were confirmed as HIV positive. Ninety (75%) of these women had both HIV-1 and HIV-2, twenty (16.7%) had only HIV-1 and 10 (8.3%) had only HIV-2. Staphylococcus aureus and Escherichia coli were the predominant bacteria. Antibiogram of the bacterial isolates determined by using the Kirby Bauer disk diffusion showed that most of them were susceptible to augmentin, gentamicin, peflacin, ciprofloxacin, ofloxacin and amoxicillin but were highly resistant to commonly used, over-the-counter drugs like chloramphenicol, tetracycline and streptomycin. This thus poses additional burden on the healthcare system in its attempt to manage HIV using anti-retroviral drugs among other methods, along with immunity enhancing drugs while the search for HIV vaccines still continues.

Synthesis and Immunological Evaluation of Pentamannose-Based HIV-1 Vaccine Candidates.

Dense glycosylation and the trimeric conformation of the human immunodeficiency virus-1 (HIV-1) envelope protein limit the accessibility of some cellular glycan processing enzymes and end up with high-mannose-type N-linked glycans on the envelope spike, among which the Man5GlcNAc2 structure occupies a certain proportion. The Man5GlcNAc2 glycan composes the binding sites of some potent broadly neutralizing antibodies, and some lectins that can bind Man5GlcNAc2 show HIV-neutralizing activity. Therefore, Man5GlcNAc2 is a potential target for HIV-1 vaccine development. Herein, a highly convergent and effective strategy was developed for the synthesis of Man5 and its monofluoro-modified, trifluoro-modified, and S-linked analogues. We coupled these haptens to carrier protein CRM197 and evaluated the immunogenicity of the glycoconjugates in mice. The serological assays showed that the native Man5 conjugates failed to induce Man5-specific antibodies in vivo, while the modified analogue conjugates induced stronger antibody responses. However, these antibodies could not bind the native gp120 antigen. These results demonstrated that the immune tolerance mechanism suppressed the immune responses to Man5-related structures and the conformation of glycan epitopes on the synthesized glycoconjugates was distinct from that of native glycan epitopes on gp120.