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Viruses May 2024Neutralizing antibodies targeting the spike (S) protein of SARS-CoV-2, elicited either by natural infection or vaccination, are crucial for protection against the virus....
Neutralizing antibodies targeting the spike (S) protein of SARS-CoV-2, elicited either by natural infection or vaccination, are crucial for protection against the virus. Nonetheless, the emergence of viral escape mutants presents ongoing challenges by contributing to breakthrough infections. To define the evolution trajectory of SARS-CoV-2 within the immune population, we co-incubated replication-competent rVSV/SARS-CoV-2/GFP chimeric viruses with sera from COVID-19 convalescents. Our findings revealed that the E484D mutation contributes to increased viral resistant against both convalescent and vaccinated sera, while the L1265R/H1271Y double mutation enhanced viral infectivity in 293T-hACE2 and Vero cells. These findings suggest that under the selective pressure of polyclonal antibodies, SARS-CoV-2 has the potential to accumulate mutations that facilitate either immune evasion or greater infectivity, facilitating its adaption to neutralizing antibody responses. Although the mutations identified in this study currently exhibit low prevalence in the circulating SARS-CoV-2 populations, the continuous and meticulous surveillance of viral mutations remains crucial. Moreover, there is an urgent necessity to develop next-generation antibody therapeutics and vaccines that target diverse, less mutation-prone antigenic sites to ensure more comprehensive and durable immune protection against SARS-CoV-2.
Topics: SARS-CoV-2; Spike Glycoprotein, Coronavirus; Humans; COVID-19; Antibodies, Neutralizing; Antibodies, Viral; Animals; Chlorocebus aethiops; Vero Cells; Mutation; Immune Evasion; HEK293 Cells
PubMed: 38793644
DOI: 10.3390/v16050763 -
Viruses Apr 2024People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral...
People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccines, but fewer studies have examined cellular immune responses to the vaccinations. Here, we used an activation-induced marker (AIM) assay to quantify SARS-CoV-2 spike-specific CD4+ and CD8+ T cells generated by two and three doses of COVID-19 vaccines in 50 PLWH receiving antiretroviral therapy, compared to 87 control participants without HIV. In a subset of PLWH, T-cell responses were also assessed after post-vaccine breakthrough infections and/or receipt of a fourth vaccine dose. All participants remained SARS-CoV-2 infection-naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to a Nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 control participants after the third vaccine dose. Multivariable regression analyses were used to investigate the relationships between sociodemographic, health- and vaccine-related variables, vaccine-induced T-cell responses, and breakthrough infection risk. We observed that a third vaccine dose boosted spike-specific CD4+ and CD8+ T-cell frequencies significantly above those measured after the second dose (all < 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose ( > 0.1), but CD8+ T-cell responses were modestly lower in PLWH after the third dose ( = 0.02), an observation that remained significant after adjusting for sociodemographic, health- and vaccine-related variables ( = 0.045). In PLWH who experienced a breakthrough infection, median T-cell frequencies increased even higher than those observed after three vaccine doses ( < 0.03), and CD8+ T-cell responses in this group remained higher even after a fourth vaccine dose ( = 0.03). In multivariable analyses, the only factor associated with an increased breakthrough infection risk was younger age, which is consistent with the rapid increase in SARS-CoV-2 seropositivity that was seen among younger adults in Canada after the initial appearance of the Omicron variant. These results indicate that PLWH receiving antiretroviral therapy mount strong T-cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection.
Topics: Humans; Male; HIV Infections; Female; COVID-19 Vaccines; Middle Aged; SARS-CoV-2; COVID-19; CD8-Positive T-Lymphocytes; Adult; CD4-Positive T-Lymphocytes; Spike Glycoprotein, Coronavirus; Antibodies, Viral; Aged; Immunity, Cellular; Breakthrough Infections
PubMed: 38793543
DOI: 10.3390/v16050661 -
Pathogens (Basel, Switzerland) Apr 2024This study aims to screen for IgG antibodies against () in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in...
This study aims to screen for IgG antibodies against () in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were examined, and a comparative evaluation of commercially available serological methods was conducted. Three methods were employed to detect IgG antibodies against : Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Antibody Test (IFAT), and Western Blot (WB), which was used as a reference here. Forty-nine sera samples were true-positive for IgG antibodies against , resulting in a 31.61% positivity rate, and the immunoassay test statistical reliability analysis resulted in higher IFAT accuracy (90.97%) compared to ELISA (76.26%). Furthermore, statistical analysis of demographic and immunological data included in the study placed female and foreign/non-Greek individuals at 2.24 ( = 0.0009) and 2.34 ( = 0.0006) times higher risk of positive IgG testing compared to their male and Greek counterparts, respectively. Our findings on positivity rates and comparative serology underscore the importance of early and suitable screening measures for newly diagnosed HIV+ patients to mitigate the life-threatening outcomes that may arise from a potential subsequent activation.
PubMed: 38787227
DOI: 10.3390/pathogens13050375 -
JCI Insight Apr 2024Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2...
Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.
Topics: Humans; HIV Infections; Male; Female; Child; Meningococcal Vaccines; Child, Preschool; Meningococcal Infections; Antibodies, Bacterial; B-Lymphocytes; Infectious Disease Transmission, Vertical; Immunogenicity, Vaccine; Immunoglobulin G
PubMed: 38775152
DOI: 10.1172/jci.insight.177182 -
Nature Communications May 2024The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs)...
The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.
Topics: Humans; AIDS Vaccines; HIV-1; HIV Antibodies; Antibodies, Neutralizing; CD4 Antigens; Vaccines, DNA; Antibodies, Monoclonal; HIV Infections; Cryoelectron Microscopy; HIV Envelope Protein gp120; Binding Sites; Complementarity Determining Regions
PubMed: 38773089
DOI: 10.1038/s41467-024-48514-8 -
Kidney International Reports Apr 2024Hepatitis B virus (HBV) vaccination is crucial for seronegative patients with advanced chronic kidney disease (CKD) for protection during dialysis while preparing for...
INTRODUCTION
Hepatitis B virus (HBV) vaccination is crucial for seronegative patients with advanced chronic kidney disease (CKD) for protection during dialysis while preparing for transplantation. A standard regimen for HBV vaccination requires 24 weeks to be completed. An accelerated HBV vaccination regimen completed within 8 weeks has shown early effective seroconversion in healthcare workers. However, data for patients with advanced CKD are limited.
METHODS
A randomized controlled trial was conducted in patients with advanced CKD (estimated glomerular filtration rate [GFR] <30 ml/min per 1.73 m) and patients on dialysis. The patients were randomly assigned to either a standard HBV vaccination regimen (Engerix B; 40 μg at 0, 4, 8, and 24 weeks) or an accelerated regimen (40 μg at 0, 1, 4, and 8 weeks). The hepatitis B surface antibodies (anti-HBs) were measured at 12, 28, and 52 weeks. Seroconversion were defined as anti-HBs ≥10 IU/l.
RESULTS
At 12 weeks, among the intention-to-treat (ITT) population of 133 participants (65 in the accelerated and 68 in the standard groups), the accelerated group demonstrated significantly higher rates of seroconversion (83.08% vs. 63.24%, = 0.01). In the per-protocol (PP) analysis of 125 patients (62 in the standard and 63 in the accelerated groups), the accelerated group exhibited higher seroconversion rate compared with the standard group (85.71% vs. 69.35%, = 0.03). At 28 and 52 weeks, the seroconversion rates were similar between the 2 groups.
CONCLUSION
In patients with advanced CKD, the accelerated HBV vaccination regimen demonstrated a significantly higher seroconversion rate at 12 weeks of vaccination. This finding suggests that the accelerated regimen is an effective option to achieve rapid seroconversion before initiating hemodialysis or before undergoing kidney transplantation.
PubMed: 38770057
DOI: 10.1016/j.ekir.2024.01.014 -
Proceedings of the National Academy of... May 2024Efforts to develop an HIV-1 vaccine include those focusing on conserved structural elements as the target of broadly neutralizing monoclonal antibodies. MAb D5 binds to...
Efforts to develop an HIV-1 vaccine include those focusing on conserved structural elements as the target of broadly neutralizing monoclonal antibodies. MAb D5 binds to a highly conserved hydrophobic pocket on the gp41 N-heptad repeat (NHR) coiled coil and neutralizes through prevention of viral fusion and entry. Assessment of 17-mer and 36-mer NHR peptides presenting the D5 epitope in rodent immunogenicity studies showed that the longer peptide elicited higher titers of neutralizing antibodies, suggesting that neutralizing epitopes outside of the D5 pocket may exist. Although the magnitude and breadth of neutralization elicited by NHR-targeting antigens are lower than that observed for antibodies directed to other epitopes on the envelope glycoprotein complex, it has been shown that NHR-directed antibodies are potentiated in TZM-bl cells containing the FcγRI receptor. Herein, we report the design and evaluation of covalently stabilized trimeric 51-mer peptides encompassing the complete gp41 NHR. We demonstrate that these peptide trimers function as effective antiviral entry inhibitors and retain the ability to present the D5 epitope. We further demonstrate in rodent and nonhuman primate immunization studies that our 51-mer constructs elicit a broader repertoire of neutralizing antibody and improved cross-clade neutralization of primary HIV-1 isolates relative to 17-mer and 36-mer NHR peptides in A3R5 and FcγR1-enhanced TZM-bl assays. These results demonstrate that sensitive neutralization assays can be used for structural enhancement of moderately potent neutralizing epitopes. Finally, we present expanded trimeric peptide designs which include unique low-molecular-weight scaffolds that provide versatility in our immunogen presentation strategy.
Topics: HIV Envelope Protein gp41; HIV-1; Animals; AIDS Vaccines; Antibodies, Neutralizing; HIV Antibodies; Humans; Mice; Epitopes; HIV Infections; Peptides; Female; Antibodies, Monoclonal
PubMed: 38768344
DOI: 10.1073/pnas.2317230121 -
PloS One 2024Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated...
Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.
Topics: Humans; Female; Papillomavirus Infections; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; Human papillomavirus 16; Human papillomavirus 18; Adult; Young Adult; Adolescent; Antibodies, Viral; Papillomavirus Vaccines; DNA, Viral; Vaccination; Cervix Uteri
PubMed: 38768231
DOI: 10.1371/journal.pone.0304080 -
PloS One 2024The burden of parallel and overlapping infections of Sexually Transmitted Infections (STIs), particularly HIV, syphilis, hepatitis B (HBV), and hepatitis C virus (HCV)...
Epidemiology of an overlapping and parallel infection of Sexually Transmitted Infections among pregnant women in North-east Ethiopia: Its implication for prevention of mother to child transmission.
BACKGROUND
The burden of parallel and overlapping infections of Sexually Transmitted Infections (STIs), particularly HIV, syphilis, hepatitis B (HBV), and hepatitis C virus (HCV) are disproportionately higher among pregnant women globally, leading to unwanted consequences. These infections pose significant public health challenges as they can be transmitted vertically to the offspring. This study aimed to determine the sero-epidemiological patterns and predictors of STIs (HIV, syphilis, HBV, and HCV) among pregnant women attending antenatal care clinics at ten health facilities in North-eastern Ethiopia.
METHODS
An institution-based multi-center cross-sectional study was conducted from May to November 2022 among 422 pregnant women selected using simple random sampling technique. Semi-structured questionnaire was used to collect socio-demographic characteristics and predictor variables of STIs through face-to-face interviews. Venous blood was collected and it was tested for anti-HIV, HBsAg, anti-HCV, and anti-Treponemal antibodies using immunochromatographic test kits. Multinomial logistic regression analysis was used to identify associated factors of STIs. Variables with an adjusted odds ratio (AOR) and a p-value <0.05 were considered statistically significant.
RESULTS
The overall prevalence of STIs was 23.9% (95% CI = 20.08-28.25). The prevalence of parallel infections of HIV, hepatitis B, hepatitis C, and syphilis were 6.4%, 9%, 1.7%, and 6.9%, respectively. The overlapping infections for HIV-HBV was 4% but HIV-HCV overlapping infection wasn't found. Increased age, tattooing, multiple sexual partners, exposure to unsafe sex, and RH status were independent factors of HBV. Likewise, increased age, rural residence, illiteracy, and tattooing were independently associated with HCV. Moreover, rural residence and a history of tattooing were independent predictors for the acquisition of HIV, whereas multiple sexual partners and RH status were found to be significant predictors of syphilis infection among pregnant women.
CONCLUSION
The magnitude of overlapping and parallel STD infections is still continued to be a problem among pregnant women. Moreover, there were overlapping infections of HBV-HIV. Therefore, continuous screening of pregnant women for HIV, syphilis, hepatitis B, and C infections should be performed, and special attention should be given to pregnant women who have co-infections.
Topics: Humans; Female; Ethiopia; Adult; Pregnancy; Cross-Sectional Studies; Sexually Transmitted Diseases; Young Adult; Pregnancy Complications, Infectious; Hepatitis B; Syphilis; Infectious Disease Transmission, Vertical; Hepatitis C; Adolescent; HIV Infections; Prevalence; Seroepidemiologic Studies
PubMed: 38768132
DOI: 10.1371/journal.pone.0300149 -
Emerging Microbes & Infections Dec 2024Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce... (Observational Study)
Observational Study
Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.
Topics: Humans; Antibodies, Viral; Male; Smallpox Vaccine; HIV Infections; Adult; Female; China; Middle Aged; Monkeypox virus; Smallpox; Vaccination; Mpox (monkeypox); Cross Reactions; Young Adult; Enzyme-Linked Immunosorbent Assay; Vaccinia virus
PubMed: 38767199
DOI: 10.1080/22221751.2024.2356153