Impact of HIV-Related Immune Impairment of Yellow Fever Vaccine Immunogenicity in People Living with HIV-ANRS 12403.

The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.

Differential gene expression of cytokines, receptors, and miRNAs in individuals living with HIV-1 and vaccinated against yellow fever.

Between 2016 and 2018, Brazil faced a yellow fever (YF) outbreak, which led to an expansion of vaccination coverage. The coexistence of the YF outbreak and the HIV-1 epidemic in Brazil raised concerns regarding the immune response and vaccine effectiveness in individuals living with HIV (PLWH). The aim of this study was to investigate the immune response to YF vaccination in PLWH and HIV-uninfected individuals as controls. Transcript levels of immunomodulatory molecules, including IL-6, IL-10, IL-21, TGF-ß, CD19, CD163, miR-21, miR-146, and miR-155, were measured using RTqPCR. TCD4+ cells were evaluated by cytometry, and neutralizing antibody (Nab) titers were detected by a micro plaque-reduction neutralization test. The findings of our study revealed several noteworthy observations. First, there was a notable reduction in the circulation of TCD4+ cells postvaccination. Among people living with HIV (PLWH), we observed an increase in the expression of IL-10 following vaccination, while IL-6 expression was diminished in PLWH with lower TCD4+ counts. Furthermore, we identified the downregulation of CD19 and TGF-ß, along with the upregulation of IL-21 and CD163. Notably, we observed positive correlations between the levels of IL-10/IL-21, IL-10/CD163, and IL-6/CD19. Additionally, there was a positive correlation between miRNAs 146 and 155. It is important to emphasize that all participants exhibited robust neutralizing antibody responses after receiving 17DD YF vaccination. In this context, the gene expression data presented can be useful for biomarker studies of protective antibodies induced by YF vaccination. This study sheds light on immune mechanisms in individuals living with HIV and YF vaccination.

The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients.

IMPORTANCE: The study provides valuable insights into the sociodemographic characteristics, clinical outcomes, and humoral immune response of those affected by the virus that has devastated every field of human life since 2019; the COVID-19 patients. Firstly, the association among clinical manifestations, comorbidities, and the production of neutralizing antibodies (Nabs) against SARS-CoV-2 is explored. Secondly, varying levels of Nabs among patients are revealed, and a significant correlation between the presence of Nabs and a shorter duration of hospitalization is identified, which highlights the potential role of Nabs in predicting clinical outcomes. Lastly, a follow-up conducted 7 months later demonstrates the progression and persistence of Nabs production in recovered unvaccinated individuals. The study contributes essential knowledge regarding the characteristics of the study population, the early humoral immune response, and the dynamics of Nabs production over time. These findings have significant implications for understanding the immune response to COVID-19 and informing clinical management approaches.

Inflammasome genes polymorphisms are associated with progression to mechanical ventilation and death in a cohort of hospitalized COVID-19 patients in a reference hospital in Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1ßrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease (WHO < 6; n = 76), and group 2 included patients with severe/critical COVID-19 (WHO ≥ 6; n = 357). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic - National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype (ORadj = 0.36; P = 0.032), allele A (ORadj = 0.93; P = 0.010), or carrier-A (ORadj = 0.45; P = 0.027) in the NLRP3 rs1539019 polymorphism; A/T genotype (ORadj = 0.5; P = 0.045), allele T (ORadj = 0.93; P = 0.018), or carrier-T (ORadj = 0.48; P = 0.029) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C (ORadj = 0.11; P = 0.018), A-C-G-C-G (ORadj = 0.23; P = 0.003), C-C-G-C-C (ORadj = 0.37; P = 0.021), and C-T-G-A-C (ORadj = 0.04; P = 0.0473) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

Chikungunya, Zika and Dengue seroprevalence rates among pregnant women in a hospital of southeastern Brazil / Soroprevalência de chikungunya, zika e dengue em gestantes de um hospital do sudeste do Brasil / Seroprevalencia de chikungunya, zika y dengue en mujeres embarazadas en un hospital del sureste de Brasil

Background and objectives: For decades, dengue outbreaks have been affecting vast territories of the Americas. In 2010's decade, Chikungunya and Zika virus (CHIKV and ZIKV) emerged as new arboviruses in the region. While several seroprevalence rates have been reported for dengue virus (DENV) infection in Brazil, serological surveys for the latest are scarce. We aimed to evaluate the seroprevalence of CHIKV, ZIKV, and DENV infections in pregnant women at admission to a public maternity hospital of Nova Iguaçu, state of Rio de Janeiro. Methods: A simple questionnaire was applied, containing limited demographic, obstetric, and clinical data, alongside with blood collection. Different commercial test kits, based on enzyme-linked immunosorbent assay (ELISA), were used. Results: Among 349 pregnant women enrolled from July to December 2017, there was a 28.4% seroreactivity for CHIKV, 47.2% for ZIKV, and 88.8% for DENV. Conclusion: These findings reflect the high dengue endemicity scenario and suggest a significant reach of the recent outbreaks of ZIKV and CHIKV infections in the region.(AU)

Justificativas e objetivos: Há décadas, surtos de dengue afetam vastos territórios das Américas. Na década de 2010, os vírus Chikungunya e Zika (CHIKV e ZIKV) surgiram como arbovírus emergentes na região. Embora diversas taxas de soroprevalência tenham sido relatadas para a infecção pelo vírus da dengue (DENV) no Brasil, pesquisas sorológicas para chikungunya e zika são escassas. Objetivou-se avaliar a soroprevalência das infecções por CHIKV, ZIKV e DENV em gestantes admitidas em uma maternidade pública de Nova Iguaçu, estado do Rio de Janeiro. Métodos: Foi aplicado um questionário simples, contendo dados demográficos, obstétricos e clínicos limitados, sendo realizada coleta de sangue na mesma visita. Diferentes kits de teste comerciais, baseados em ensaio imunoenzimático (ELISA), foram utilizados. Resultados: De 349 gestantes recrutadas de julho a dezembro de 2017, houve sororreatividade de 28,4% para CHIKV, 47,2% para ZIKV e 88,8% para DENV. Conclusão: Esses achados refletem o cenário de alta endemicidade da dengue e sugerem um alcance significativo dos surtos recentes causados por ZIKV e CHIKV na região.(AU)

Justificación y objetivos: Durante décadas, los brotes de dengue han afectado a vastos territorios de las Américas. En la década de 2010, los virus Chikungunya y Zika (CHIKV y ZIKV) surgieron como arbovirus emergentes en la región. Aunque se han reportadas varias tasas de seroprevalencia para la infección por el virus del dengue (DENV) en Brasil, la investigación serológica para el chikungunya y el Zika es escasa. Este estudio tuvo como objetivo evaluar la seroprevalencia de infecciones por CHIKV, ZIKV y DENV en mujeres embarazadas ingresadas en una maternidad pública en Nova Iguaçu, estado de Rio de Janeiro. Métodos: Se aplicó un sencillo cuestionario, que contenía datos demográficos, obstétricos y clínicos limitados, y se extrajo sangre en la misma visita. Se utilizaron diferentes kits de prueba comerciales basados en el ensayo inmunoabsorbente ligado a enzimas (ELISA). Resultados: De 349 mujeres embarazadas reclutadas de julio a diciembre de 2017, hubo serorreactividad de 28,4% para CHIKV, 47,2% para ZIKV y 88,8% para DENV. Conclusión: Estos hallazgos reflejan el escenario de alta endemicidad para el dengue y sugieren una variedad significativa de brotes recientes causados por ZIKV y CHIKV en la región.(AU)

Chikungunya, Zika and Dengue seroprevalence rates among pregnant women in a hospital of southeastern Brazil / Soroprevalência de chikungunya, zika e dengue em gestantes de um hospital do sudeste do Brasil

Justificativas e objetivos: Há décadas, surtos de dengue afetam vastos territórios das Américas. Na década de 2010, os vírus Chikungunya e Zika (CHIKV e ZIKV) surgiram como arbovírus emergentes na região. Embora diversas taxas de soroprevalência tenham sido relatadas para a infecção pelo vírus da dengue (DENV) no Brasil, pesquisas sorológicas para chikungunya e zika são escassas. Objetivou-se avaliar a soroprevalência das infecções por CHIKV, ZIKV e DENV em gestantes admitidas em uma maternidade pública de Nova Iguaçu, estado do Rio de Janeiro. Métodos: Foi aplicado um questionário simples, contendo dados demográficos, obstétricos e clínicos limitados, sendo realizada coleta de sangue na mesma visita. Diferentes kits de teste comerciais, baseados em ensaio imunoenzimático (ELISA), foram utilizados. Resultados: De 349 gestantes recrutadas de julho a dezembro de 2017, houve sororreatividade de 28,4% para CHIKV, 47,2% para ZIKV e 88,8% para DENV. Conclusão: Esses achados refletem o cenário de alta endemicidade da dengue e sugerem um alcance significativo dos surtos recentes causados por ZIKV e CHIKV na região.

Cross-Neutralizing Antibodies in HIV-1 Individuals Infected by Subtypes B, F1, C or the B/Bbr Variant in Relation to the Genetics and Biochemical Characteristics of the env Gene.

Various HIV-1 env genetic and biochemical features impact the elicitation of cross-reactive neutralizing antibodies in natural infections. Thus, we aimed to investigate cross-neutralizing antibodies in individuals infected with HIV-1 env subtypes B, F1, C or the B/Bbr variant as well as env characteristics. Therefore, plasma samples from Brazilian chronically HIV-1 infected individuals were submitted to the TZM-bl neutralization assay. We also analyzed putative N-glycosylation sites (PNGLs) and the size of gp120 variable domains in the context of HIV-1 subtypes prevalent in Brazil. We observed a greater breadth and potency of the anti-Env neutralizing response in individuals infected with the F1 or B HIV-1 subtypes compared with the C subtype and the variant B/Bbr. We observed greater V1 B/Bbr and smaller V4 F1 than those of other subtypes (p<0.005), however neither was there a correlation verified between the variable region length and neutralization potency, nor between PNLG and HIV-1 subtypes. The enrichment of W at top of V3 loop in weak neutralizing response viruses and the P in viruses with higher neutralization susceptibility was statistically significant (p = 0.013). Some other signatures sites were associated to HIV-1 subtype-specific F1 and B/Bbr samples might influence in the distinct neutralizing response. These results indicate that a single amino acid substitution may lead to a distinct conformational exposure or load in the association domain of the trimer of gp120 and interfere with the induction power of the neutralizing response, which affects the sensitivity of the neutralizing antibody and has significant implications for vaccine design.

Short communication: neutralizing antibodies in HIV-1-infected Brazilian individuals.

Tests for the detection of the humoral immune response to HIV-1 have to be standardized and established, demanding regional efforts. For this purpose the neutralizing antibody (NAb) assay for HIV-1 in TZM-bl cells was introduced in Brazil. Twenty plasma samples from HIV-1-infected individuals were assayed: 10 progressors and 10 long-term nonprogressors. These were tested against eight env-pseudotyped viruses (psVs) in the TZM-bl NAb assay and against HIV-1 strain HTLV/IIIB (HIV-1 IIIB) in primary lymphocytes. Forty-four percent of the samples showed neutralizing titers for psVs and 55% for HIV-1 IIIB. Plasma from progressors showed a broader neutralization and a higher potency. The introduction of these reference reagents encourages the participation of Brazil in future comparative assessments of anti-HIV-1 antibodies.