Specific antibody responses to Qß-displayed Plasmodium falciparum-derived UB05 and MSP3 proteins in mother-neonate couples.

Malaria blood-stage parasite is a critical pathogenic stage responsible for serious adverse outcomes in pregnant women and their neonates. Immunoglobulin G (IgG) antibody responses specific to various asexual blood-stage antigens were well reported in non-pregnant individuals. However, little is still known during placental malaria. To assess the antibody responses specific to Plasmodium falciparum-derived MSP3 and UB05 malaria vaccine candidates in mother-neonate couples, mother's peripheral blood and neonate's cord blood samples were collected at delivery. After malaria diagnostic, plasma levels of IgG and IgG subclass responses specific to UB05, MSP3 and UB05-MSP3 were determined using ELISA. As outcomes, both mothers and neonates had significantly higher IgG responses to UB05 and UB05-MSP3 compared to anti-MSP3 IgG (p < 0.05), irrespective of malaria status. Significant negative correlations were observed between IgG levels specific to the three antigens and parasitaemia (p < 0.01). Anti-UB05 and anti-UB05-MSP3 IgG levels in neonates showed a significant positive correlation with the corresponding mothers' antibodies (rs = 0.25 with p = 0.04; rs = 0.31 with p = 0.01, respectively). UB05MSP3-specific IgG3 and IgG1 subclass responses were significantly higher than the IgG4 subclass (p < 0.01). The neonates IgG1 and IgG3 levels positively correlated with the corresponding antibody subclasses of mothers. These findings suggest an association between UB05 and UB05-MSP3-specific antibody responses and malaria control during pregnancy. Maternal-foetal transfer of MSP3 and UB05-specific IgG occurs during pregnancy, suggesting the interest in the future malaria vaccination strategies in pregnant women to generate early protective immunity in baby against malaria.

High vaccine effectiveness against severe COVID-19 outcomes and population preventable fraction during the Omicron era in Luxembourg: A nationwide retrospective risk factor analysis.

BACKGROUND: Luxembourg experienced major consecutive SARS-CoV-2 infection waves due to Omicron variants during 2022 while having achieved a high vaccination coverage in 2021. We investigated the risk factors associated to severe outcomes (i.e., hospitalisation, deaths) and estimated vaccine effectiveness (VE) as well as the role of immunity conferred by prior infections against severe outcomes in adults. METHODS: We linked reported SARS-CoV-2 cases among residents aged ≥ 20 years with vaccination data and SARS-CoV-2 related hospitalisations and deaths. Cases were followed-up until day 14 for COVID-19 related hospital admission and up to day 28 for mortality after a positive test. We analysed the association between the vaccination status and severe forms using proportional Cox regression, adjusting for previous infection, age, sex and nursing homes residency. VE was measured as 1-adjusted hazard ratio of vaccinated vs unvaccinated individuals. The population preventable fraction was computed using the adjusted hazard ratio and the proportion of cases within the vaccination category. RESULTS: Between December 2021, and March 2023, we recorded 187143 SARS-CoV-2 cases, 1728 (0.93%) hospitalizations and 611 (0.33%) deaths. The risk of severe outcomes increased with age, was higher among men and nursing home residents. Compared to unvaccinated adults, VE against hospitalization was 38.8% (95%CI: 28.1%-47.8%) for a complete primary cycle of vaccination, 62.1% (95%CI: 57.0%-66.7%) for one booster, and 71.6% (95%CI: 66.7%-76.2%) for two booster doses. VE against death was respectively 49.5% (95%CI: 30.8%-63.3%), 69.0% (95%CI: 61.2%-75.3%) and 76.2% (95%CI: 68.4%-82.2%). Previous infection was not associated with lower risk of hospitalisation or mortality. The vaccination lowered mortality by 55.8 % (95%CI: 46.3%-62.8%) and reduced hospital admissions by 49.1% (95%CI: 43.4%-54.4%). CONCLUSIONS: Complete vaccination and booster but not previous infection were protective against hospitalization and death. The vaccination program in Luxembourg led to substantial reductions in SARS-CoV-2-related mortality and hospitalizations at the population level.

Therapeutic landscape in systemic lupus erythematosus: mtDNA activation of the cGAS-STING pathway.

Mitochondrial DNA (mtDNA) serves as a pivotal immune stimulus in the immune response. During stress, mitochondria release mtDNA into the cytoplasm, where it is recognized by the cytoplasmic DNA receptor cGAS. This activation initiates the cGAS-STING-IRF3 pathway, culminating in an inflammatory response. The cGAS-STING pathway has emerged as a critical mediator of inflammatory responses in microbial infections, stress, autoimmune diseases, chronic illnesses, and tissue injuries. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by connective tissue involvement across various bodily systems. Its hallmark is the production of numerous autoantibodies, which prompt the immune system to target and damage the body's own tissues, resulting in organ and tissue damage. Increasing evidence implicates the cGAS-STING pathway as a significant contributor to SLE pathogenesis. This article aims to explore the role of the mtDNA-triggered cGAS-STING pathway and its mechanisms in SLE, with the goal of providing novel insights for clinical interventions.

Disruption of IL-17-mediated immunosurveillance in the respiratory mucosa results in invasive Streptococcus pyogenes infection.

Introduction: Streptococcus pyogenes is a Gram-positive pathogen that causes a significant global burden of skin pyoderma and pharyngitis. In some cases, infection can lead to severe invasive streptococcal diseases. Previous studies have shown that IL-17 deficiency in mice (IL-17-/-) can reduce S. pyogenes clearance from the mucosal surfaces. However, the effect of IL-17 on the development of severe invasive streptococcal disease has not yet been assessed. Methods: Here, we modeled single or repeated non-lethal intranasal (IN) S. pyogenes M1 strain infections in immunocompetent and IL-17-/- mice to assess bacterial colonization following a final IN or skin challenge. Results: Immunocompetent mice that received a single S. pyogenes infection showed long-lasting immunity to subsequent IN infection, and no bacteria were detected in the lymph nodes or spleens. However, in the absence of IL-17, a single IN infection resulted in dissemination of S. pyogenes to the lymphoid organs, which was accentuated by repeated IN infections. In contrast to what was observed in the respiratory mucosa, skin immunity did not correlate with the systemic levels of IL-17. Instead, it was found to be associated with the activation of germinal center responses and accumulation of neutrophils in the spleen. Discussion: Our results demonstrated that IL-17 plays a critical role in preventing invasive disease following S. pyogenes infection of the respiratory tract.

RNF138 Downregulates Antiviral Innate Immunity by Inhibiting IRF3 Activation.

A viral infection activates the transcription factors IRF3 and NF-κB, which synergistically induces type I interferons (IFNs). Here, we identify the E3 ubiquitin ligase RNF138 as an important negative regulator of virus-triggered IRF3 activation and IFN-ß induction. The overexpression of RNF138 inhibited the virus-induced activation of IRF3 and the transcription of the IFNB1 gene, whereas the knockout of RNF138 promoted the virus-induced activation of IRF3 and transcription of the IFNB1 gene. We further found that RNF138 promotes the ubiquitination of PTEN and subsequently inhibits PTEN interactions with IRF3, which is essential for the PTEN-mediated nuclear translocation of IRF3, thereby inhibiting IRF3 import into the nucleus. Our findings suggest that RNF138 negatively regulates virus-triggered signaling by inhibiting the interaction of PTEN with IRF3, and these data provide new insights into the molecular mechanisms of cellular antiviral responses.

Association of naturally acquired type-specific HPV antibodies and subsequent HPV re-detection: systematic review and meta-analysis.

BACKGROUND: Understanding the role of naturally acquired (i.e., infection-induced) human papillomavirus (HPV) antibodies against reinfection is important given the high incidence of this sexually transmitted infection. However, the protective effect of naturally acquired antibodies in terms of the level of protection, duration, and differential effect by sex remains incompletely understood. We conducted a systematic review and a meta-analysis to (1) strengthen the evidence on the association between HPV antibodies acquired through past infection and subsequent type-specific HPV detection, (2) investigate the potential influence of type-specific HPV antibody levels, and (3) assess differential effects by HIV status. METHODS: We searched Embase and Medline databases to identify studies which prospectively assessed the risk of type-specific HPV detection by baseline homologous HPV serostatus among unvaccinated individuals. Random-effect models were used to pool the measures of association of naturally acquired HPV antibodies against subsequent incident detection and persistent HPV positivity. Sources of heterogeneity for each type were assessed through subgroup analyses stratified by sex, anatomical site of infection, male sexual orientation, age group, and length of follow-up period. Evidence of a dose-response relationship of the association between levels of baseline HPV antibodies and type-specific HPV detection was assessed. Finally, we pooled estimates from publications reporting associations between HPV serostatus and type-specific HPV detection by baseline HIV status. RESULTS: We identified 26 publications (16 independent studies, with 62,363 participants) reporting associations between baseline HPV serostatus and incident HPV detection, mainly for HPV-16 and HPV-18, the most detected HPV type. We found evidence of protective effects of baseline HPV seropositivity and subsequent detection of HPV DNA (0.70, 95% CI 0.61-0.80, NE = 11) and persistent HPV positivity (0.65, 95% CI 0.42-1.01, NE = 5) mainly for HPV-16 among females, but not among males, nor for HPV-18. Estimates from 8 studies suggested a negative dose-response relationship between HPV antibody level and subsequent detection among females. Finally, we did not observe any differential effect by baseline HIV status due to the limited number of studies available. CONCLUSION: We did not find evidence that naturally acquired HPV antibodies protect against subsequent HPV positivity in males and provide only modest protection among females for HPV-16. One potential limitation to the interpretation of these findings is potential misclassification biases due to different causes.

Updated roles of cGAS-STING signaling in autoimmune diseases.

Natural immunity, the first line for the body to defense against the invasion of pathogen, serves as the body's perception of the presence of pathogens depends on nucleic acid recognition mechanisms. The cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) signaling pathway is considered an essential pattern recognition and effector pathway in the natural immune system and is mainly responsible for recognizing DNA molecules present in the cytoplasm and activating downstream signaling pathways to generate type I interferons and some other inflammatory factors. STING, a crucial junction protein in the innate immune system, exerts an essential role in host resistance to external pathogen invasion. Also, STING, with the same character of inflammatory molecules, is inseparable from the body's inflammatory response. In particular, when the expression of STING is upregulated or its related signaling pathways are overactivated, the body may develop serious infectious disorders due to the generation of excessive inflammatory responses, non-infectious diseases, and autoimmune diseases. In recent years, accumulating studies indicated that the abnormal activation of the natural immune cGAS-STING signaling pathway modulated by the nucleic acid receptor cGAS closely associated with the development and occurrence of autoimmune diseases (AID). Thereof, to explore an in-depth role of STING and its related signaling pathways in the diseases associated with inflammation may be helpful to provide new avenues for the treatment of these diseases in the clinic. This article reviews the activation process of the cGAS-STING signaling pathways and its related important roles, and therapeutic drugs in AID, aiming to improve our understanding of AID and achieve better diagnosis and treatment of AID.

Estimating the cumulative incidence of SARS-CoV-2 infection in Costa Rica: modelling seroprevalence data in a population-based cohort.

Background: The true incidence of SARS-CoV-2 infection in Costa Rica was likely much higher than officially reported, because infection is often associated with mild symptoms and testing was limited by official guidelines and socio-economic factors. Methods: Using serology to define natural infection, we developed a statistical model to estimate the true cumulative incidence of SARS-CoV-2 in Costa Rica early in the pandemic. We estimated seroprevalence from 2223 blood samples collected from November 2020 to October 2021 from 1976 population-based controls from the RESPIRA study. Samples were tested for antibodies against SARS-CoV-2 nucleocapsid and the receptor-binding-domain of the spike proteins. Using a generalized linear model, we estimated the ratio of true infections to officially reported cases. Applying these ratios to officially reported totals by age, sex, and geographic area, we estimated the true number of infections in the study area, where 70% of Costa Ricans reside. We adjusted the seroprevalence estimates for antibody decay over time, estimated from 1562 blood samples from 996 PCR-confirmed COVID-19 cases. Findings: The estimated total proportion infected (ETPI) was 4.0 times higher than the officially reported total proportion infected (OTPI). By December 16th, 2021, the ETPI was 47% [42-52] while the OTPI was 12%. In children and adolescents, the ETPI was 11.0 times higher than the OTPI. Interpretation: Our findings suggest that nearly half the population had been infected by the end of 2021. By the end of 2022, it is likely that a large majority of the population had been infected. Funding: This work was sponsored and funded by the National Institute of Allergy and Infectious Diseases through the National Cancer Institute, the Science, Innovation, Technology and Telecommunications Ministry of Costa Rica, and Costa Rican Biomedical Research Agency-Fundacion INCIENSA (grant N/A).

COVID-19 Infection Rates in Vaccinated and Unvaccinated Inmates: A Retrospective Cohort Study.

Background In 2023, breakthrough COVID-19 infections among vaccinated individuals and reinfections in previously infected people have become common. Additionally, infections are due to Omicron subvariants of the virus that behave differently from those at the onset of the pandemic. Understanding how vaccination and natural immunity influence COVID-19 infection rates is crucial, especially in high-density congregate settings such as prisons, to inform public health strategies. Methods We analyzed COVID-19 surveillance data from January to July 2023 across 33 California state prisons, primarily a male population of 96,201 individuals. We computed the incidence rate of new COVID-19 infections among COVID-bivalent-vaccinated and entirely unvaccinated groups (those not having received either the bivalent or monovalent vaccine). Results Our results indicate that the infection rates in the bivalent-vaccinated and entirely unvaccinated groups are 3.24% (95% confidence interval (CI): 3.06-3.42%) and 2.72% (CI: 2.50-2.94%), respectively, with an absolute risk difference of only 0.52%. When the data were filtered for those aged 50 and above, the infection rates were 4.07% (CI: 3.77-4.37%) and 3.1% (CI: 2.46-3.74%), respectively, revealing a mere 0.97% absolute risk difference. Among those aged 65 and above, the infection rates were 6.45% (CI: 5.74-7.16%) and 4.5% (CI: 2.57-6.43%), respectively, with an absolute risk difference of 1.95%. Conclusion We note low infection rates in both the vaccinated and unvaccinated groups, with a small absolute difference between the two across age groups. A combination of monovalent and bivalent vaccines and natural infections likely contributed to immunity and a lower level of infection rates compared to the height of the pandemic. It is possible that a degree of 'herd immunity' has been achieved. Yet, using p<0.05 as the threshold for statistical significance, the bivalent-vaccinated group had a slightly but statistically significantly higher infection rate than the unvaccinated group in the statewide category and the age ≥50 years category. However, in the older age category (≥65 years), there was no significant difference in infection rates between the two groups. This suggests that while the bivalent vaccine might offer protection against severe outcomes, it may not significantly reduce the risk of infections entirely. Further research is needed to understand the reasons behind these findings and to consider other factors, such as underlying health conditions. This study underscores the importance of developing vaccines that target residual COVID-19 infections, especially in regard to evolving COVID-19 variants.

The Influence of Sex Hormones and X Chromosome in Immune Responses.

Males and females differ in their susceptibility to develop autoimmunity and allergy but also in their capacity to cope with infections and cancers. Cellular targets and molecular pathways underlying sexual dimorphism in immunity have started to emerge and appeared multifactorial. It became increasingly clear that sex-linked biological factors have important impact on the development, tissue maintenance and effector function acquisition of distinct immune cell populations, thereby regulating multiple layers of innate or adaptive immunity through distinct mechanisms. This review discusses the recent development in our understanding of the cell-intrinsic actions of biological factors linked to sex, sex hormones and sex chromosome complement, on immune cells, which may account for the sex differences in susceptibility to autoimmune diseases and allergies, and the sex-biased responses in natural immunity and cancer.

Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity.

BACKGROUND: Studies comparing SARS-CoV-2 reinfection outcomes among individuals with previous infection (natural immunity) and previous infection plus vaccination (hybrid immunity) are limited. METHODS: Retrospective cohort study comparing SARS-CoV-2 reinfection among patients with hybrid immunity (cases) and natural immunity (controls) from March 2020 to February 2022. Reinfection was defined as positive PCR> 90 days after initial laboratory-confirmed SARS-CoV-2 infection. Outcomes included time to reinfection, symptom severity, COVID-19-related hospitalization, critical COVID-19 illness (need for intensive care unit, invasive mechanical ventilation, or death), length of stay (LOS). RESULTS: A total of 773 (42%) vaccinated and 1073 (58%) unvaccinated patients with reinfection were included. Most patients (62.7%) were asymptomatic. Median time to reinfection was longer with hybrid immunity (391 [311-440] vs 294 [229-406] days, p < 0.001). Cases were less likely to be symptomatic (34.1% vs 39.6%, p = 0.001) or develop critical COVID-19 (2.3% vs 4.3%, p = 0.023). However, there was no significant difference in rates of COVID-19-related hospitalization (2.6% vs 3.8%, p = 0.142) or LOS (5 [2-9] vs 5 [3-10] days, p = 0.446). Boosted patients had longer time to reinfection (439 [IQR 372-467] vs 324 [IQR 256-414] days, p < 0.001) and were less likely to be symptomatic (26.8% vs 38%, p = 0.002) compared to unboosted patients. Rates of hospitalization, progression to critical illness and LOS were not significantly different between the two groups. CONCLUSIONS: Natural and hybrid immunity provided protection against SARS-CoV-2 reinfection and hospitalization. However, hybrid immunity conferred stronger protection against symptomatic disease and progression to critical illness and was associated with longer time to reinfection. The stronger protection conferred by hybrid immunity against severe outcomes due to COVID-19 should be emphasized with the public to further the vaccination effort, especially in high-risk individuals.

Dynamics of Naturally Acquired Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 in Children and Adolescents.

OBJECTIVE: To evaluate the duration of protection against reinfection conferred by a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. STUDY DESIGN: We applied 2 complementary approaches: a matched test-negative, case-control design and a retrospective cohort design. A total of 458 959 unvaccinated individuals aged 5-18 years were included. The analyses focused on the period July 1, 2021, to December 13, 2021, a period of Delta variant dominance in Israel. We evaluated 3 SARS-CoV-2-related outcomes: documented polymerase chain reaction-confirmed infection or reinfection, symptomatic infection or reinfection, and SARS-CoV-2-related hospitalization or death. RESULTS: Overall, children and adolescents who were previously infected acquired durable protection against reinfection with SARS-CoV-2 for at least 18 months. Importantly, no SARS-CoV-2-related deaths were recorded in either the SARS-CoV-2-naïve group or the previously infected group. The effectiveness of naturally acquired immunity against a recurrent infection reached 89.2% (95% CI, 84.7%-92.4%) at 3-6 months after the first infection and declined slightly to 82.5% (95% CI, 79.1%-85.3%) by 9-12 months after infection, with a slight nonsignificant waning trend seen up to 18 months after infection. Additionally, children aged 5-11 years exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in those aged 12-18 years was more prominent but still mild. CONCLUSIONS: Children and adolescents who were previously infected with SARS-CoV-2 remain protected to a high degree for 18 months. Further research is needed to examine naturally acquired immunity against Omicron and newer emerging variants.

Liver-stage Plasmodium infection tunes clinical outcomes.

Chora and colleagues show that infection of the liver by Plasmodium modulates severity of disease in the experimental cerebral malaria (ECM) model by generating gamma delta (ɣδ) T cells that produce IL-17. This work calls into question the long-standing assumption that liver infection does not modulate severity of malaria.

Antibodies to repeat-containing antigens in Plasmodium falciparum are exposure-dependent and short-lived in children in natural malaria infections.

Protection against Plasmodium falciparum, which is primarily antibody-mediated, requires recurrent exposure to develop. The study of both naturally acquired limited immunity and vaccine induced protection against malaria remains critical for ongoing eradication efforts. Towards this goal, we deployed a customized P. falciparum PhIP-seq T7 phage display library containing 238,068 tiled 62-amino acid peptides, covering all known coding regions, including antigenic variants, to systematically profile antibody targets in 198 Ugandan children and adults from high and moderate transmission settings. Repeat elements - short amino acid sequences repeated within a protein - were significantly enriched in antibody targets. While breadth of responses to repeat-containing peptides was twofold higher in children living in the high versus moderate exposure setting, no such differences were observed for peptides without repeats, suggesting that antibody responses to repeat-containing regions may be more exposure dependent and/or less durable in children than responses to regions without repeats. Additionally, short motifs associated with seroreactivity were extensively shared among hundreds of antigens, potentially representing cross-reactive epitopes. PfEMP1 shared motifs with the greatest number of other antigens, partly driven by the diversity of PfEMP1 sequences. These data suggest that the large number of repeat elements and potential cross-reactive epitopes found within antigenic regions of P. falciparum could contribute to the inefficient nature of malaria immunity.

Critical assessment of the impact of vaccine-type and immunity on the burden of COVID-19.

The COVID-19 pandemic continues to have a devastating impact on health systems and economies across the globe. Implementing public health measures in tandem with effective vaccination strategies have been instrumental in curtailing the burden of the pandemic. With the three vaccines authorized for use in the U.S. having varying efficacies and waning effects against major COVID-19 strains, understanding the impact of these vaccines on COVID-19 incidence and fatalities is critical. Here, we formulate and use mathematical models to assess the impact of vaccine type, vaccination and booster uptake, and waning of natural and vaccine-induced immunity on the incidence and fatalities of COVID-19 and to predict future trends of the disease in the U.S. when existing control measures are reinforced or relaxed. The results show a 5-fold reduction in the control reproduction number during the initial vaccination period and a 1.8-fold (2-fold) reduction in the control reproduction number during the initial first booster (second booster) uptake period, compared to the respective previous periods. Due to waning of vaccine-induced immunity, vaccinating up to 96% of the U.S. population might be required to attain herd immunity, if booster uptake is low. Additionally, vaccinating and boosting more people from the onset of vaccination and booster uptake, especially with the Pfizer-BioNTech and Moderna vaccines (which confer superior protection than the Johnson & Johnson vaccine) would have led to a significant reduction in COVID-19 cases and deaths in the U.S. Furthermore, adopting natural immunity-boosting measures is important in fighting COVID-19 and transmission rate reduction measures such as mask-use are critical in combating COVID-19. The emergence of a more transmissible COVID-19 variant, or early relaxation of existing control measures can lead to a more devastating wave, especially if transmission rate reduction measures and vaccination are relaxed simultaneously, while chances of containing the pandemic are enhanced if both vaccination and transmission rate reduction measures are reinforced simultaneously. We conclude that maintaining or improving existing control measures, and boosting with mRNA vaccines are critical in curtailing the burden of the pandemic in the U.S.

Initiation of the alternative pathway of complement and the history of "tickover".

The evolutionary history of complement suggests that the alternative pathway arose prior to the arrival of the classical and lectin pathways. In these pathways, target specificity is provided by antibodies and sugar specific lectins. While these efficient initiation systems dominate activation on most targets, the alternative pathway produces most of the C3b and 80%-90% of the C5b-9. While the tickover process, originally proposed by Peter Lachmann, provided ancient hosts with a crude self/non-self-discriminatory system that initiated complement attack on everything foreign, tickover clearly plays a more minor role in complement activation in modern organisms possessing classical and lectin pathways. Spontaneous activation of the alternative pathway via tickover may play a major role in human pathologies where tissue damage is complement-mediated. The molecular mechanism of tickover is still not convincingly proven. Prevailing hypotheses include (a) spontaneous hydrolysis of the thioester in C3 forming the C3b-like C3(H2 O) in solution and (b) "enhanced tickover" in which surfaces cause specific or non-specific contact activated conformational changes in C3. Theoretical considerations, including computer simulations, suggest that the latter mechanism is more likely and that more research needs to be devoted to understanding interactions between biological surfaces and C3.

Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination.

BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.

SARS-CoV-2-The Role of Natural Immunity: A Narrative Review.

BACKGROUND: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. AIMS: This narrative review analyzes the literature regarding these two immunitary processes and more specifically: (a) the duration of natural immunity; (b) cellular immunity; (c) cross-reactivity; (d) the duration of post-vaccination immune protection; (e) the probability of reinfection and its clinical manifestations in the recovered patients; (f) the comparisons between vaccinated and unvaccinated as to the possible reinfections; (g) the role of hybrid immunity; (h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; (i) the comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. MATERIAL AND METHODS: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. RESULTS: nearly 900 studies were collected, and 246 pertinent articles were included. It was highlighted that the vast majority of the individuals after suffering from COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. CONCLUSIONS: this extensive narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Consequently, vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: (a) measure the durability of immunity over time; (b) evaluate both the impacts of Omicron BA.5 on vaccinated and healed subjects and the role of hybrid immunity.

Wasteosomes (corpora amylacea) of human brain can be phagocytosed and digested by macrophages.

BACKGROUND: Corpora amylacea of human brain, recently renamed as wasteosomes, are granular structures that appear during aging and also accumulate in specific areas of the brain in neurodegenerative conditions. Acting as waste containers, wasteosomes are formed by polyglucosan aggregates that entrap and isolate toxic and waste substances of different origins. They are expelled from the brain to the cerebrospinal fluid (CSF), and can be phagocytosed by macrophages. In the present study, we analyze the phagocytosis of wasteosomes and the mechanisms involved in this process. Accordingly, we purified wasteosomes from post-mortem extracted human CSF and incubated them with THP-1 macrophages. Immunofluorescence staining and time-lapse recording techniques were performed to evaluate the phagocytosis. We also immunostained human hippocampal sections to study possible interactions between wasteosomes and macrophages at central nervous system interfaces. RESULTS: We observed that the wasteosomes obtained from post-mortem extracted CSF are opsonized by MBL and the C3b complement protein. Moreover, we observed that CD206 and CD35 receptors may be involved in the phagocytosis of these wasteosomes by THP-1 macrophages. Once phagocytosed, wasteosomes become degraded and some of the resulting fractions can be exposed on the surface of macrophages and interchanged between different macrophages. However, brain tissue studies show that, in physiological conditions, CD206 but not CD35 receptors may be involved in the phagocytosis of wasteosomes. CONCLUSIONS: The present study indicates that macrophages have the machinery required to process and degrade wasteosomes, and that macrophages can interact in different ways with wasteosomes. In physiological conditions, the main mechanism involve CD206 receptors and M2 macrophages, which trigger the phagocytosis of wasteosomes without inducing inflammatory responses, thus avoiding tissue damage. However, altered wasteosomes like those obtained from post-mortem extracted CSF, which may exhibit waste elements, become opsonized by MBL and C3b, and so CD35 receptors constitute another possible mechanism of phagocytosis, leading in this case to inflammatory responses.

Pre-Pandemic Cross-Reactive Immunity against SARS-CoV-2 among Central and West African Populations.

For more than two years after the emergence of COVID-19 (Coronavirus Disease-2019), significant regional differences in morbidity persist. These differences clearly show lower incidence rates in several regions of the African and Asian continents. The work reported here aimed to test the hypothesis of a pre-pandemic natural immunity acquired by some human populations in central and western Africa, which would, therefore, pose the hypothesis of an original antigenic sin with a virus antigenically close to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To identify such pre-existing immunity, sera samples collected before the emergence of COVID-19 were tested to detect the presence of IgG reacting antibodies against SARS-CoV-2 proteins of major significance. Sera samples from French blood donors collected before the pandemic served as a control. The results showed a statistically significant difference of antibodies prevalence between the collected samples in Africa and the control samples collected in France. Given the novelty of our results, our next step consists in highlighting neutralizing antibodies to evaluate their potential for pre-pandemic protective acquired immunity against SARS-CoV-2. In conclusion, our results suggest that, in the investigated African sub-regions, the tested populations could have been potentially and partially pre-exposed, before the COVID-19 pandemic, to the antigens of a yet non-identified Coronaviruses.