-
The Journal of Infectious Diseases Jun 2024Bivalent mRNA vaccines, designed to combat emerging SARS-CoV-2 variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in...
BACKGROUND
Bivalent mRNA vaccines, designed to combat emerging SARS-CoV-2 variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination.
METHODS
Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months post vaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/ml (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics.
RESULTS
In SHCS participants, baseline anti-spike antibody concentrations ≥1642 were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a five-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events.
CONCLUSIONS
Bivalent mRNA vaccination elicited a robust humoral response in individuals with HIV or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare.
PubMed: 38848312
DOI: 10.1093/infdis/jiae291 -
Romanian Journal of Internal Medicine =... Jun 2024Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with...
INTRODUCTION
Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients.
CASE PRESENTATION
We present the case of a 29-year-old female patient with HIV and end-stage renal disease (ESRD) who performed a KT from a related living donor in March 2022. KT immediate evolution was favorable. No transplant-related complications were reported. HIV viral load remained undetectable and CD4+ T cells were constantly > 500 cell/ μL, during the 18 months of follow-up. The main challenge in our case was the drug interaction between the protease inhibitor-based regimen and tacrolimus. This led to tacrolimus overdose, and, subsequently, change in ARV therapy. ARV switching was performed on a regimen based on integrase inhibitor and nucleoside reverse transcriptase inhibitors. After the ARV change, the therapeutic level of tacrolimus was easily reached and maintained. Kidney graft function remained normal during follow-up, despite tacrolimus overexposure, and no rejection or anti-HLA antibodies were observed. Another challenge was related to the donor's hepatitis C virus status (positive antibodies, negative nucleic acid test). The recipient did not develop seroconversion or detectable viremia at 3-, 6-, 12- and 18-months post-KT.
CONCLUSION
We reported the first case of a successful KT in an ESRD patient with HIV in Romania, in whom the post-transplant evolution was favorable.
PubMed: 38848262
DOI: 10.2478/rjim-2024-0020 -
Cell Reports Jun 2024The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B...
The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.
Topics: Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Antibodies, Neutralizing; COVID-19; Epitopes; Antibodies, Viral; Antibodies, Monoclonal; Animals; Betacoronavirus; Mice
PubMed: 38848216
DOI: 10.1016/j.celrep.2024.114307 -
Vaccine Jun 2024Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between...
BACKGROUND
Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored.
AIM
To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens.
METHOD
The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels.
RESULTS
The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05).
CONCLUSION
The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.
PubMed: 38845303
DOI: 10.1016/j.vaccine.2024.06.010 -
Current Opinion in HIV and AIDS Jul 2024Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy... (Review)
Review
PURPOSE OF REVIEW
Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies.
RECENT FINDINGS
During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials.
SUMMARY
Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.
Topics: Humans; HIV Infections; Immunotherapy; Animals; Child; Macaca mulatta; Disease Models, Animal; Infant; Simian Immunodeficiency Virus; AIDS Vaccines
PubMed: 38841850
DOI: 10.1097/COH.0000000000000857 -
Blood Jun 2024Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is...
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP, receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the two cohorts (3 and 4 days; P = 0.31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B co-infection, an ovarian teratoma with associated anti-platelet antibodies, and multiple platelet transfusion before the correct diagnosis may have impeded immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.
PubMed: 38838300
DOI: 10.1182/blood.2023023780 -
BMC Research Notes Jun 2024Fourth-generation HIV Ag/Ab Combo assay is used for HIV screening of blood for transfusion in developing countries, however, the sensitivity of the assay is questionable...
OBJECTIVE
Fourth-generation HIV Ag/Ab Combo assay is used for HIV screening of blood for transfusion in developing countries, however, the sensitivity of the assay is questionable during the acute phase of HIV infection. Thus, the study aimed to determine the effect of combining centrifugation with HIV-1 virion lysis on the sensitivity of the fourth-generation HIV Ag/Ab combo assay.
RESULTS
When the 50 HIV-1 antibody-negative samples were run on the fourth-generation HIV Ag/Ab combo assay, 8 (16%) were positive following centrifugation, 13 (26%) were positive following lysis while 25 (50%) were positive after combining centrifugation with HIV-1 virion lysis.
Topics: HIV-1; Humans; Centrifugation; HIV Infections; HIV Antibodies; Sensitivity and Specificity; Virion; HIV Antigens
PubMed: 38835056
DOI: 10.1186/s13104-024-06810-y -
Journal of Clinical Virology : the... Aug 2024A global mpox outbreak occurred in 2022, and a domestic outbreak started in South Korea in April 2023. This study aimed to evaluate the clinical characteristics, viral...
BACKGROUND
A global mpox outbreak occurred in 2022, and a domestic outbreak started in South Korea in April 2023. This study aimed to evaluate the clinical characteristics, viral shedding, and immune response of mpox in South Korea.
METHODS
Patients hospitalized with mpox in the National Medical Center between September 2022 and June 2023 were included in this study. Oropharyngeal (OP), anogenital lesion (AL), and skin lesion (SL) swabs and blood samples were collected, and monkeypox virus (MPXV) DNA using real-time polymerase chain reaction (RT-PCR) and culture assays were performed. Neutralizing antibodies (NAbs) against MPXV A.2.1, B.1.1, and B.1.3 were detected using plaque reduction neutralization tests.
RESULTS
Eighteen patients were enrolled, of whom 17 (94.4 %) were male, with a median (IQR) age of 32.5 (24-51) years. While nine (50 %) were HIV-infected individuals, none of them revealed CD4+ counts less than 200 cells/μL. MPXV DNA was detected in 87.3 % and 82.7 % of patient's ALs and SLs, respectively, until 2 weeks after symptom onset. While MPXV was isolated for up to 15 days in all three sample types, the culture positivity decreased to 53.8 % and 42.9 % in ALs and SLs after 10 days, respectively, and 28.6 % and 22.2 %, respectively, after 2 weeks from symptom onset. The NAb titers against MPXV A.2.1 were significantly lower than those against B.1.1 and B.1.3.
CONCLUSIONS
Infectious MPXV was isolated from various anatomical sites up to 15 days after symptom onset. The MPXV NAb response was varied among different lineages, and this implies limited cross-lineage protection.
Topics: Humans; Male; Female; Adult; Republic of Korea; Antibodies, Neutralizing; Middle Aged; Virus Shedding; Young Adult; Antibodies, Viral; Disease Outbreaks; DNA, Viral
PubMed: 38830304
DOI: 10.1016/j.jcv.2024.105692 -
Heliyon Jun 2024To monitor post-vaccination antibody production, neutralizing activity, and their dynamics over time in people living with HIV (PLWH).
OBJECTIVE
To monitor post-vaccination antibody production, neutralizing activity, and their dynamics over time in people living with HIV (PLWH).
METHODS
We collected sera from 147 PLWH and 94 healthy controls after vaccination at different time points and examined changes in antibody levels and neutralizing activity using enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization assay.
RESULTS
IgG levels were substantially increased in both PLWH and healthy controls after the booster injection. Antibody levels decreased significantly in both PLWH and controls five months after the booster injection. However, the rate of decrease was not significantly different between the two groups. The generated antibodies demonstrated protective efficacy against the wild-type SARS-CoV-2 strain, but very low protection against the mutant strains. Furthermore, the protection decreased over time. The vaccine was less effective in PLWH with <200/μl CD4 T cells. During the SARS-CoV-2 recovery period, participants had substantially increased serum antibody levels and protective efficacy compared with those who received the booster.
CONCLUSION
Both PLWH and controls demonstrated comparable antibody production ability. Vaccines and booster development against SARS-CoV-2 mutant strains should be prioritized in PLWH, especially in those with low CD4 counts.
PubMed: 38828333
DOI: 10.1016/j.heliyon.2024.e31731 -
Therapeutic Advances in Infectious... 2024Syphilis is a serious global public health challenge. Despite prior progress in syphilis control, incidence has been increasing in recent years. Syphilis is a common...
BACKGROUND
Syphilis is a serious global public health challenge. Despite prior progress in syphilis control, incidence has been increasing in recent years. Syphilis is a common coinfection among people living with HIV (PLHIV). In Panama, few data describe syphilis prevalence among PLHIV. We describe syphilis antibody and high-titer (⩾1:8) active syphilis prevalence and associated factors among individuals who attended an antiretroviral clinic.
METHODS
A cross-sectional study was undertaken during February-March 2022 and September-October 2022 for adults (⩾18 year) assigned male and female at birth, respectively. Participants provided peripheral blood samples and self-administered a questionnaire. Samples were screened using immunochromatography; antibody-positive samples were tested using rapid plasma regain to 1:512 dilutions. Logistic regression was used to identify factors associated with syphilis antibody and high-titer active syphilis.
RESULTS
In all, 378 participants gave blood samples; 377 individuals participated in the questionnaire (216 self-reported male sex [males], 158 female [females], and three intersex individuals). Median age was 36 years (interquartile range: 28-45 years). Overall, syphilis antibody prevalence was 32.3% (122/378) (males, 50.7% [108/2013]; females, 5.7% [9/158]; intersex individuals, 100.0% (3/3)], < 0.01. High-titer active syphilis was found among 24.6% ( = 30) of samples with positive antibody test (males 27.8% [ = 30], females 0.0% [0/9], intersex individuals 0.0% [0/3]). Antibody positivity was associated in the multivariable model with males (50.7%, AOR = 24.6, 95%CI: 1.57-384.53). High-titer active syphilis was associated with younger participant age (18-30 years, 13.2%, OR = 4.82, 95%CI: 1.17-19.83); 31-40 years, 7.8%, OR = 4.24, 95%CI: 1.04-17.21 3.2% >40 years), homosexual identity (16.0% OR = 34.2, 95%CI: 4.50-259.27 0.6% among heterosexual identity); in the multivariable model, associated with sexual identity (bisexual 19.1%, AOR = 10.89, 95%CI: 1.00-119.06) compared to heterosexual identity (0.6%) and weakly associated with concurrency (⩾1 ongoing sexual relationships, 15.9%, AOR = 3.09, 95%CI: 0.94-10.14).
CONCLUSION
This study found very high prevalence of syphilis antibodies and high-titer syphilis among PLHIV in Panama. Those most affected are males, younger in age, those who practice concurrent sexual relationships, and those who reported homosexual and bisexual identity. Targeted interventions should include repetitive testing and treatment, especially among individuals who may be at increased infection risk.
PubMed: 38827952
DOI: 10.1177/20499361241256290