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Trends in Immunology Jun 2024The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key... (Review)
Review
The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa.
PubMed: 38890026
DOI: 10.1016/j.it.2024.05.005 -
Journal of Medical Virology Jun 2024Human immunodeficiency virus (HIV) infection is still a global public health issue, and the development of an effective prophylactic vaccine inducing potent neutralizing...
Human immunodeficiency virus (HIV) infection is still a global public health issue, and the development of an effective prophylactic vaccine inducing potent neutralizing antibodies remains a significant challenge. This study aims to explore the inflammation-related proteins associated with the neutralizing antibodies induced by the DNA/rTV vaccine. In this study, we employed the Olink chip to analyze the inflammation-related proteins in plasma in healthy individuals receiving HIV candidate vaccine (DNA priming and recombinant vaccinia virus rTV boosting) and compared the differences between neutralizing antibody-positive (nab + ) and -negative(nab-) groups. We identified 25 differentially expressed factors and conducted enrichment and correlation analysis on them. Our results revealed that significant expression differences in artemin (ARTN) and C-C motif chemokine ligand 23 (CCL23) between nab+ and -nab- groups. Notably, the expression of CCL23 was negatively corelated to the ID of neutralizing antibodies and the intensity of the CD4 T cell responses. This study enriches our understanding of the immune picture induced by the DNA/rTV vaccine, and provides insights for future HIV vaccine development.
Topics: Humans; Antibodies, Neutralizing; Vaccinia virus; HIV Antibodies; HIV-1; Adult; Proteomics; AIDS Vaccines; Male; HIV Infections; Vaccines, DNA; Female; Healthy Volunteers; Vaccines, Synthetic; Plasma; Young Adult
PubMed: 38888113
DOI: 10.1002/jmv.29749 -
Nature Biotechnology Jun 2024
Topics: Humans; AIDS Vaccines; HIV Infections; HIV Antibodies; HIV-1; Antibodies, Neutralizing; Broadly Neutralizing Antibodies
PubMed: 38886609
DOI: 10.1038/s41587-024-02289-x -
Nature Immunology Jun 2024Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8 T cell functions, which requires a deeper understanding of CD8 T cells...
Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8 T cell functions, which requires a deeper understanding of CD8 T cells promoting HIV control. Here we identifiy an antigen-responsive TOXTCF1CD39CD8 T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8 T cells and proteomic analysis of purified CD8 T cell subsets identified TOXTCF1CD39CD8 T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXTCF1CD39CD8 T cells were found at higher frequency than TCF1CD39CD8 T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOXTCF1CD39CD8 T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8 T cells contributes to limiting SIV and HIV persistence.
PubMed: 38886592
DOI: 10.1038/s41590-024-01875-0 -
JCI Insight Jun 2024Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is confounded by several...
Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is confounded by several factors, including reactive CD4+ T cell proliferation, and further provides no specificity information. We circumvented these limitations by selectively depleting CD8+ T cells specific for the Gag epitope CTPYDINQM (CM9) via the administration of immunotoxin-conjugated tetrameric complexes of CM9/Mamu-A*01. Immunotoxin administration effectively depleted circulating but not tissuelocalized CM9-specific CD8+ T cells, akin to the bulk depletion pattern observed with antibodies directed against CD8. However, we found no evidence to indicate that circulating CM9-specific CD8+ T cells suppressed viral replication in Mamu-A*01+ rhesus macaques during acute or chronic progressive infection with a pathogenic strain of SIV. This observation extended to macaques with established infection during and after continuous antiretroviral therapy. In contrast, natural controller macaques experienced dramatic increases in plasma viremia after immunotoxin administration, highlighting the importance of CD8+ T cell-mediated immunity against CM9. Collectively, these data showed that CM9-specific CD8+ T cells were necessary but not sufficient for robust immune control of SIV in a nonhuman primate model and, more generally, validated an approach that could inform the design of next-generation vaccines against HIV-1.
PubMed: 38885329
DOI: 10.1172/jci.insight.174168 -
Frontiers in Medicine 2024The rapid changes in the coronavirus genomes created new strains after the first variation was found in Wuhan in 2019. SARS-CoV-2 genotypes should periodically undergo...
PURPOSE
The rapid changes in the coronavirus genomes created new strains after the first variation was found in Wuhan in 2019. SARS-CoV-2 genotypes should periodically undergo whole genome sequencing to control it because it has been extremely helpful in combating the virus. Many diagnoses, treatments, and vaccinations have been developed against it based on genome sequencing. With its practical implications, this study aimed to determine changes in the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic by genome sequencing, thereby providing crucial insights for developing effective control strategies that can be directly applied in the field.
DESIGN
We meticulously generated 17 high-quality whole-genome sequence data from 48 SARS-CoV-2 genotypes of COVID-19 patients who tested positive by PCR in Tashkent, Uzbekistan. Our rigorous approach, which includes stringent quality control measures and multiple rounds of verification, ensures the accuracy and reliability of our findings.
METHODS
Our study employed a unique combination of genome sequencing and bioinformatics web tools to analyze amino acid (AA) changes in the virus genomes. This approach allowed us to understand the genetic changes in the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic.
RESULTS
Our study revealed significant nucleotide polymorphisms, including non-synonymous (missense) and synonymous mutations in the coding regions of the sequenced sample genomes. These findings, categorized by phylogenetic analysis into the G clade (or GK sub-clade), contribute to our understanding of the delta variant of SARS-CoV-2 widespread in Uzbekistan during the pandemic. A total of 134 mutations were identified, consisting of 65 shared and 69 unique mutations. These nucleotide changes, including one frameshift mutation, one conservative and disruptive insertion-deletion, four upstream region mutations, four downstream region mutations, 39 synonymous mutations, and 84 missense mutations, are crucial in the ongoing battle against the virus.
CONCLUSION
The comprehensive whole-genome sequencing data presented in this study aids in tracing the origins and sources of circulating SARS-CoV-2 variants and analyzing emerging variations within Uzbekistan and globally. The genome sequencing of SARS-CoV-2 from samples collected in Uzbekistan in late 2021, during the peak of the pandemic's second wave nationwide, is detailed here. Following acquiring these sequences, research efforts have focused on developing DNA and plant-based edible vaccines utilizing prevalent SARS-CoV-2 strains in Uzbekistan, which are currently undergoing clinical trials.
PubMed: 38882660
DOI: 10.3389/fmed.2024.1401655 -
MedComm Jun 2024Spike-protein-based pseudotyped viruses were used to evaluate vaccines during the COVID-19 pandemic. However, they cannot be used to evaluate the envelope (E), membrane...
Spike-protein-based pseudotyped viruses were used to evaluate vaccines during the COVID-19 pandemic. However, they cannot be used to evaluate the envelope (E), membrane (M), and nucleocapsid (N) proteins. The first generation of virus-like particle (VLP) pseudotyped viruses contains these four structural proteins, but their titers for wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relatively low, even lower for the omicron variant, rendering them unsuitable for neutralizing antibody detection. By optimizing the spike glycoprotein signal peptide, substituting the complexed M and E proteins with SARS-COV-1, optimizing the N protein with specific mutations (P199L, S202R, and R203M), and truncating the packaging signal, PS9, we increased the titer of the wild-type VLP pseudotyped virus over 100-fold, and successfully packaged the omicron VLP pseudotyped virus. The SARS-CoV-2 VLP pseudotyped viruses maintained stable titers, even through 10 freeze-thaw cycles. The key neutralization assay parameters were optimized, including cell type, cell number, and viral inoculum. The assay demonstrated minimal variation in both intra- and interassay results, at 11.5% and 11.1%, respectively. The correlation between the VLP pseudotyped virus and the authentic virus was strong ( = 0.9). Suitable for high-throughput detection of various mutant strains in clinical serum. In summary, we have developed a reliable neutralization assay for SARS-CoV-2 based on VLP pseudotyped virus.
PubMed: 38881676
DOI: 10.1002/mco2.615 -
Biochemistry. Biokhimiia May 2024Antigenic cartography is a tool for interpreting and visualizing antigenic differences between virus variants based on virus neutralization data. This approach has been... (Review)
Review
Antigenic cartography is a tool for interpreting and visualizing antigenic differences between virus variants based on virus neutralization data. This approach has been successfully used in the selection of influenza vaccine seed strains. With the emergence of SARS-CoV-2 variants escaping vaccine-induced antibody response, adjusting COVID-19 vaccines has become essential. This review provides information on the antigenic differences between SARS-CoV-2 variants revealed by antigenic cartography and explores a potential of antigenic cartography-based methods (e.g., building antibody landscapes and neutralization breadth gain plots) for the quantitative assessment of the breadth of the antibody response. Understanding the antigenic differences of SARS-CoV-2 and the possibilities of the formed humoral immunity aids in the prompt modification of preventative vaccines against COVID-19.
Topics: Humans; SARS-CoV-2; COVID-19; Antibodies, Viral; COVID-19 Vaccines; Antigens, Viral; Spike Glycoprotein, Coronavirus; Antibodies, Neutralizing
PubMed: 38880647
DOI: 10.1134/S0006297924050079 -
Microbial Pathogenesis Jun 2024Bacteria-derived outer membrane vesicles (OMVs) can be engineered to incorporate foreign antigens. This study explored the potential of ClearColi™-derived OMVs as a...
Bacteria-derived outer membrane vesicles (OMVs) can be engineered to incorporate foreign antigens. This study explored the potential of ClearColi™-derived OMVs as a natural adjuvant and a carrier (recombinant OMVs or rOMVs) for development of an innovative therapeutic vaccine candidate harboring HIV-1 Nef and Nef-Tat antigens. Herein, the rOMVs containing CytolysinA (ClyA)-Nef and ClyA-Nef-Tat fusion proteins were isolated from ClearColi™ strain. The presence of Nef and Nef-Tat proteins on their surface (rOMV and rOMV) was confirmed by western blotting after proteinase K treatment. Immune responses induced by Nef and Nef-Tat proteins emulsified with Montanide® ISA720 or mixed with OMVs, and also rOMV and rOMV were investigated in BALB/c mice. Additionally, the potency of splenocytes exposed to single-cycle replicable (SCR) HIV-1 virions was assessed for the secretion of cytokines in vitro. Our findings showed that the rOMVs as an antigen carrier (rOMV and rOMV) induced higher levels of IgG2a, IFN-γ and granzyme B compared to OMVs as an adjuvant (Nef + OMV and Nef-Tat + OMV), and also Montanide® ISA720 (Nef + Montanide and Nef-Tat + Montanide). Moreover, IFN-γ level in splenocytes isolated from mice immunized with rOMV was higher than other regimens after exposure to SCR virions. Generally, ClearColi™-derived rOMVs can serve as potent carriers for developing effective vaccines against HIV-1 infection.
PubMed: 38879140
DOI: 10.1016/j.micpath.2024.106749 -
Patient Education and Counseling May 2024This study explored patients and providers' perspectives on therapeutic vaccines for cervical cancer and assessed barriers and facilitators.
OBJECTIVE
This study explored patients and providers' perspectives on therapeutic vaccines for cervical cancer and assessed barriers and facilitators.
METHODS
Qualitative semi-structured in-depth interviews were conducted with patients who had cervical dysplasia, or a past or current cervical cancer diagnosis and providers who provided care to patients with cervical abnormalities or cervical cancer. Data were analyzed using thematic analysis in NVivo.
RESULTS
A total of 28 in-depth interviews were conducted with patients (N = 15) and providers (N = 13). Participants in both groups expressed enthusiasm for the prospect of a therapeutic vaccine for cervical cancer and were encouraged by less invasive treatment opportunities. Perceived patient barriers included concerns about side effects, eligibility criteria, costs, transportation, and logistical obstacles. Providers echoed these concerns, highlighted additional structural barriers such as racism and limited availability of culturally sensitive educational aids, and underscored the need for provider training on this topic.
CONCLUSION
Our results reinforce the need for future multi-level interventions discussing vaccine efficacy, durability, and safety, as well as addressing factors such as awareness, knowledge, and beliefs.
PRACTICE IMPLICATIONS
Our findings can contribute to the development of provider and patient-centered tools that promote therapeutic vaccine acceptance.
PubMed: 38878586
DOI: 10.1016/j.pec.2024.108338