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International Journal of Infectious... Jun 2024The 2022 mpox epidemic reached a peak in Belgium and the rest of Europe in July 2022, after which it unexpectedly subsided. This study investigates epidemiological,...
OBJECTIVE
The 2022 mpox epidemic reached a peak in Belgium and the rest of Europe in July 2022, after which it unexpectedly subsided. This study investigates epidemiological, behavioral, and immunological factors behind the waning of the epidemic in Belgium.
METHODS
We investigated temporal evolutions in the characteristics and behavior of mpox patients using national surveillance data and data from a prospective registry of mpox patients in the Institute of Tropical Medicine (Antwerp). We studied behavioral changes in the population at risk using a survey among HIV-pre-exposure prophylaxis (PrEP) users. We determined the seroprevalence of anti-orthopoxvirus antibodies among HIV-PrEP users across four time points in 2022.
RESULTS
Mpox patients diagnosed at the end of the epidemic had less sexual risk behavior compared to those diagnosed earlier: they engaged less in sex at mass events, had fewer sexual partners and were less likely to belong to the sexual network's central group. Among HIV-PrEP users there were no notable changes in sexual behavior. Anti-orthopoxvirus seroprevalence did not notably increase before the start of national vaccination campaigns.
CONCLUSION
The observed changes in group immunity and behavior in the population at greater risk of exposure to mpox seem unable to explain the waning of the mpox epidemic. A change in the profile of mpox patients might have contributed to the decline in cases.
PubMed: 38942168
DOI: 10.1016/j.ijid.2024.107132 -
Virology Jun 2024An important approach to stopping the AIDS epidemic is the development of a vaccine that elicits antibodies that block virus capture, the initial interactions of HIV-1...
An important approach to stopping the AIDS epidemic is the development of a vaccine that elicits antibodies that block virus capture, the initial interactions of HIV-1 with the target cells, and replication. We utilized a previously developed qRT-PCR-based assay to examine the effects of broadly neutralizing antibodies (bNAbs), plasma from vaccine trials, and monoclonal antibodies (mAbs) on virus capture and replication. A panel of bNAbs inhibited primary HIV-1 replication in PBMCs but not virus capture. Plasma from RV144 and RV305 trial vaccinees demonstrated inhibition of virus capture with the HIV-1 subtype prevalent in Thailand. Several RV305 derived V2-specific mAbs inhibited virus replication. One of these RV305 derived V2-specific mAbs inhibited both virus capture and replication, demonstrating that it is possible to elicit antibodies by vaccination that inhibit virus capture and replication. Induction of a combination of such antibodies may be the key to protection from HIV-1 acquisition.
PubMed: 38941746
DOI: 10.1016/j.virol.2024.110158 -
Boletin Medico Del Hospital Infantil de... 2024HIV-infected children have a higher risk of presenting infections, including the hepatitis A virus (HAV). The inactivated HAV vaccine is immunogenic in immunocompetent...
BACKGROUND
HIV-infected children have a higher risk of presenting infections, including the hepatitis A virus (HAV). The inactivated HAV vaccine is immunogenic in immunocompetent hosts; however, there are insufficient studies on the duration of seroprotection in HIV-infected children.
METHODS
An analytical cohort study was conducted. HIV-1-infected children who received the inactivated HAV vaccine (2 doses) were included. Blood samples were taken for antibody measurement, the first one 28 days after the second dose and another 7 years after the vaccination schedule. Information on viral load, immunological category, weight, height, and response to antiretroviral treatment from diagnosis to the last assessment was obtained.
RESULTS
19 patients were included, with a mean age of 12.6 years (SD ± 2.29). 58% were male. 80% of the patients presented protective immunoglobulin G antibodies against HAV 7-year post-vaccination. The antibody concentration was found to be between 13 and 80 mIU/mL (median of 80 mIU/mL). 52% showed some degree of immunosuppression. There was no statistically significant relationship between the presence of seroprotection and viral load, treatment failure, immunological category, and malnutrition. Twelve patients presented with antiretroviral treatment failure, and in 33% of them, the antibodies did not offer satisfactory seroprotection.
CONCLUSION
7-year post-vaccination, 80% of HIV-infected children maintain seroprotection titers against HAV.
Topics: Humans; Male; HIV Infections; Child; Hepatitis A Vaccines; Female; Hepatitis A Antibodies; Adolescent; Hepatitis A; Cohort Studies; Viral Load; Time Factors; Follow-Up Studies; Immunoglobulin G; Vaccines, Inactivated
PubMed: 38941633
DOI: 10.24875/BMHIM.23000125 -
PloS One 2024Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and...
Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and risk factors remain limited in sub-Saharan Africa. In Ghana, HCV-related deaths are estimated to have increased since 2015. Risk factors associated with HCV infection in Ghana are not well described. The aim of this study was to determine the prevalence of, and risk factors associated with hepatitis C virus infection in the Upper East Region located in the northern part of Ghana. A community-based cross-sectional study was conducted in 9 communities in the Upper East region of Ghana. A total of 1,769 participants aged ≥12 years were screened for HCV antibody (anti-HCV) using rapid diagnostic testing (RDT). Seventy-four participants undertook HCV RNA testing after a positive anti-HCV result. Multivariate logistic regression was used to determine risk factors associated with HCV seropositivity. The anti-HCV prevalence was 8.4%, with 149 out of 1,769 testing anti-HCV positive. Mean age (±SD) of seropositive persons was 45.4 (±16.3) years. The highest anti-HCV seroprevalence was amongst persons aged 60 years and above. Forty-four out of 74 (59.5%) seropositive cases had viremic infection and the estimated viremic prevalence in the screened population was 5.0%. Predictors of HCV seropositivity were age (OR 1.03 95% CI 1.01-1.04), history of female genital mutilation or circumcision (OR 1.63 95% CI 1.04-2.55), sexual activity (OR 2.57 95% CI 1.38-4.79), positive maternal HCV status (OR 10.38 95% CI 4.13-26.05) and positive HIV status (OR 4.03 95% CI 1.35-12.05). In conclusion, the Upper East Region demonstrates a high Hepatitis C antibody prevalence. Almost 60% of individuals have viremic infection, however the cost of RNA testing is a barrier to virological diagnosis. There is a need to educate the population about HCV-associated risk factors to reduce HCV transmission and burden of disease.
Topics: Humans; Ghana; Female; Male; Middle Aged; Cross-Sectional Studies; Risk Factors; Adult; Hepatitis C; Prevalence; Hepacivirus; Young Adult; Seroepidemiologic Studies; Adolescent; Hepatitis C Antibodies; Aged; Child
PubMed: 38941280
DOI: 10.1371/journal.pone.0306292 -
Annals of Intensive Care Jun 2024A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early...
Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024.
BACKGROUND
A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients.
METHODS
The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI).
RESULTS
During the study period (November 2022-January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21).
CONCLUSIONS
Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.
PubMed: 38940865
DOI: 10.1186/s13613-024-01319-w -
Vaccines Jun 2024Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and...
Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies, and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. Overall, 29.8% of PLWH had no SARS-CoV-2 serologic markers; they displayed significantly lower CD4 counts and higher HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG ( = 0.0003), anti-S IgA ( < 0.0001) and lack of neutralizing activity against the Omicron variant ( < 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immune responses but retained specific cellular immunity.
PubMed: 38932392
DOI: 10.3390/vaccines12060663 -
Viruses Jun 2024Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through the unrelated hepatitis B virus (HBV), but...
Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through the unrelated hepatitis B virus (HBV), but with essentially inconclusive results. To try to shed light on this still-debated topic, 146 anti-HCV-positive subjects (of whom 91 HCV/HIV co-infected, and 43 with prior HCV eradication) were screened for anti-HDV antibodies (anti-HD), after careful selection for negativity to any serologic or virologic marker of current or past HBV infection. One single HCV/HIV co-infected patient (0.7%) tested highly positive for anti-HD, but with no positive HDV-RNA. Her husband, in turn, was a HCV/HIV co-infected subject with a previous contact with HBV. While conducting a thorough review of the relevant literature, the authors attempted to exhaustively describe the medical history of both the anti-HD-positive patient and her partner, believing it to be the key to dissecting the possible complex mechanisms of HDV transmission from one subject to another, and speculating that in the present case, it may have been HCV itself that behaved as an HDV helper virus. In conclusion, this preliminary research, while needing further validation in large prospective studies, provided some further evidence of a role of HCV in HDV dissemination in humans.
Topics: Humans; Hepatitis D; Hepatitis Delta Virus; Hepacivirus; Female; Hepatitis C; Coinfection; Male; Helper Viruses; Hepatitis Antibodies; Adult; Middle Aged; HIV Infections; RNA, Viral; Hepatitis B
PubMed: 38932284
DOI: 10.3390/v16060992 -
Viruses Jun 2024The envelope glycoprotein (Env) of retroviruses, such as the Feline leukemia virus (FeLV), is the main target of neutralizing humoral response, and therefore, a...
The envelope glycoprotein (Env) of retroviruses, such as the Feline leukemia virus (FeLV), is the main target of neutralizing humoral response, and therefore, a promising vaccine candidate, despite its reported poor immunogenicity. The incorporation of mutations that stabilize analogous proteins from other viruses in their prefusion conformation (e.g., HIV Env, SARS-CoV-2 S, or RSV F glycoproteins) has improved their capability to induce neutralizing protective immune responses. Therefore, we have stabilized the FeLV Env protein following a strategy based on the incorporation of a disulfide bond and an Ile/Pro mutation (SOSIP) previously used to generate soluble HIV Env trimers. We have characterized this SOSIP-FeLV Env in its soluble form and as a transmembrane protein present at high density on the surface of FeLV Gag-based VLPs. Furthermore, we have tested its immunogenicity in DNA-immunization assays in C57BL/6 mice. Low anti-FeLV Env responses were detected in SOSIP-FeLV soluble protein-immunized animals; however, unexpectedly no responses were detected in the animals immunized with SOSIP-FeLV Gag-based VLPs. In contrast, high humoral response against FeLV Gag was observed in the animals immunized with control Gag VLPs lacking SOSIP-FeLV Env, while this response was significantly impaired when the VLPs incorporated SOSIP-FeLV Env. Our data suggest that FeLV Env can be stabilized as a soluble protein and can be expressed in high-density VLPs. However, when formulated as a DNA vaccine, SOSIP-FeLV Env remains poorly immunogenic, a limitation that must be overcome to develop an effective FeLV vaccine.
Topics: Animals; Mice; Antibodies, Viral; Antibodies, Neutralizing; Mice, Inbred C57BL; Viral Envelope Proteins; Leukemia Virus, Feline; Gene Products, gag; Female; Vaccines, Virus-Like Particle; Humans; Cats; Viral Vaccines; Immunogenicity, Vaccine
PubMed: 38932278
DOI: 10.3390/v16060987 -
Viruses Jun 2024The HIV envelope glycoprotein (Env) is a trimeric protein that facilitates viral binding and fusion with target cells. As the sole viral protein on the HIV surface, Env...
The HIV envelope glycoprotein (Env) is a trimeric protein that facilitates viral binding and fusion with target cells. As the sole viral protein on the HIV surface, Env is important both for immune responses to HIV and in vaccine designs. Targeting Env in clinical applications is challenging due to its heavy glycosylation, high genetic variability, conformational camouflage, and its low abundance on virions. Thus, there is a critical need to better understand this protein. Flow virometry (FV) is a useful methodology for phenotyping the virion surface in a high-throughput, single virion manner. To demonstrate the utility of FV to characterize Env, we stained HIV virions with a panel of 85 monoclonal antibodies targeting different regions of Env. A broad range of antibodies yielded robust staining of Env, with V3 antibodies showing the highest quantitative staining. A subset of antibodies tested in parallel on viruses produced in CD4 T cell lines, HEK293T cells, and primary cells showed that the cellular model of virus production can impact Env detection. Finally, in addition to being able to highlight Env heterogeneity on virions, we show FV can sensitively detect differences in Env conformation when soluble CD4 is added to virions before staining.
Topics: Humans; env Gene Products, Human Immunodeficiency Virus; HIV-1; Virion; HEK293 Cells; HIV Antibodies; Antibodies, Monoclonal; CD4-Positive T-Lymphocytes; HIV Infections
PubMed: 38932227
DOI: 10.3390/v16060935 -
Viruses Jun 2024Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally,... (Review)
Review
BACKGROUND
Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection.
OBJECTIVE
This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals.
MAIN FINDINGS
Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a "proof of concept" for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.
Topics: Humans; HIV Infections; HIV-1; HIV Antibodies; Antibodies, Neutralizing; Immunization, Passive; Broadly Neutralizing Antibodies; Anti-HIV Agents; Animals
PubMed: 38932203
DOI: 10.3390/v16060911