HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women

Objectives: Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses.Methods: In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens: Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer.Results: Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2.Conclusions: We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children

Plasmodium falciparum and helminth coinfections Increase IgE and parasite-specific IgG responses

Coinfection with Plasmodium falciparum and helminths may impact the immune response to these parasites because they induce different immune profiles. We studied the effects of coinfections on the antibody profile in a cohort of 715 Mozambican children and adults using the Luminex technology with a panel of 16 antigens from P. falciparum and 11 antigens from helminths (Ascaris lumbricoides, hookworm, Trichuris trichiura, Strongyloides stercoralis, and Schistosoma spp.) and measured antigen-specific IgG and total IgE responses. We compared the antibody profile between groups defined by P. falciparum and helminth previous exposure (based on serology) and/or current infection (determined by microscopy and/or qPCR). In multivariable regression models adjusted by demographic, socioeconomic, water, and sanitation variables, individuals exposed/infected with P. falciparum and helminths had significantly higher total IgE and antigen-specific IgG levels, magnitude (sum of all levels) and breadth of response to both types of parasites compared to individuals exposed/infected with only one type of parasite (P ≤ 0.05). There was a positive association between exposure/infection with P. falciparum and exposure/infection with helminths or the number of helminth species, and vice versa (P ≤ 0.001). In addition, children coexposed/coinfected tended (P = 0.062) to have higher P. falciparum parasitemia than those single exposed/infected. Our results suggest that an increase in the antibody responses in coexposed/coinfected individuals may reflect higher exposure and be due to a more permissive immune environment to infection in the host. IMPORTANCE Coinfection with Plasmodium falciparum and helminths may impact the immune response to these parasites because they induce different immune profiles. We compared the antibody profile between groups of Mozambican individuals defined by P. falciparum and helminth previous exposure and/or current infection. Our results show a significant increase in antibody responses in individuals coexposed/coinfected with P. falciparum and helminths in comparison with individuals exposed/infected with only one of these parasites, and suggest that this increase is due to a more permissive immune environment to infection in the host. Importantly, this study takes previous exposure into account, which is particularly relevant in endemic areas where continuous infections imprint and shape the immune system. Deciphering the implications of coinfections deserves attention because accounting for the real interactions that occur in nature could improve the design of integrated disease control strategies

Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain.

Background: Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach. Methods: Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020. Results: Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. Conclusion: Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique.

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors

Persistence and baseline determinants of seropositivity and reinfection rates in health care workers up to 12.5 months after COVID-19

We assessed the duration and baseline determinants of antibody responses to SARS-CoV-2 spike antigens and the occurrence of reinfections in a prospective cohort of 173 Spanish primary health care worker patients followed initially for 9 months and subsequently up to 12.5 months after COVID-19 symptoms onset. Seropositivity to SARS-CoV-2 spike and receptor-binding domain antigens up to 149-270 days was 92.49% (90.17% IgG, 76.3% IgA, 60.69% IgM). In a subset of 64 health care workers who had not yet been vaccinated by April 2021, seropositivity was 96.88% (95.31% IgG, 82.81% IgA) up to 322-379 days post symptoms onset. Four suspected reinfections were detected by passive case detection, two among seronegative individuals (5 and 7 months after the first episode), and one low antibody responder. Antibody levels significantly correlated with fever, hospitalization, anosmia/hypogeusia, allergies, smoking, and occupation. Stable sustainment of IgG responses raises hope for long-lasting COVID-19 vaccine immunity

Evaluation of antibody serology to determine current helminth and plasmodium falciparum infections in a co-endemic area in Southern Mozambique

BackgroundSoil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure.MethodologyWe evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference.Principal findingsIgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure although sensitivity could not be assessed.ConclusionsWe provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers have potential good specificity as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens