Pfizer-BioNTech vaccine induces the production of cross-reactive antibodies against Trypanosoma cruzi proteins: A preliminary study.

OBJECTIVE: To evaluate the presence of cross-reactivity by anti-severe acute respiratory syndrome coronavirus 2 antibodies induced by the Pfizer-BioNTech vaccine against Trypanosoma cruzi proteins in a screening test. METHODS: Forty-three serum samples were obtained from personnel at the Hospital General Naval de Alta Especialidad in Mexico City who received one or two doses of the vaccine and were tested for T. cruzi infection using four tests: two 'in house' enzyme-linked immunosorbent assays (ELISAs), a commercial ELISA diagnostic kit and an immunoblot test. RESULTS: IgG antibodies against the T. cruzi proteins were present in the serum of unvaccinated subjects and subjects who had received one or two doses of the vaccine. The positivity of the samples against T. cruzi was ruled out by means of a Western Blot assay, where all samples were negative for T. cruzi. CONCLUSION: The data suggest that people convalescing from coronavirus disease 2019 and those who received the Pfizer-BioNTech vaccine exhibit cross-reactive antibodies against T. cruzi antigens in ELISA assays.

A Molecular Analysis of Memory B Cell and Antibody Responses Against Plasmodium falciparum Merozoite Surface Protein 1 in Children and Adults From Uganda.

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum (Pf) merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against Pf develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, full-length Pf merozoite surface protein 1 (PfMSP1FL), in individuals from a region in Uganda with high Pf transmission. Our results showed that PfMSP1FL-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ PfMSP1FL-specific classical MBCs. In contrast, anti-PfMSP1FL plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against PfMSP1FL, with broadening of the response against non-3D7 strains in adults. The B cell receptors encoded by PfMSP1FL-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable PfMSP1 protein. Proteomics analysis of PfMSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to B cell receptors of PfMSP1FL-specific MBCs, anti-PfMSP119 IgGs had high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the PfMSP1-specific humoral immune response with cumulative Pf exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of PfMSP1 variants by the plasma IgG repertoire.

Is latent Toxoplasma gondii infection associated with the occurrence of schizophrenia? A case-control study.

INTRODUCTION: Neurotropic pathogens such as Toxoplasma gondii (T. gondii) which result in chronic infections in the brain are associated with mental illnesses. In view of this, a growing body of literature has revealed the possible interaction of schizophrenia and T. gondii infection. METHOD: A case-control study was conducted from February 2018 to January 2019 among 47 Schizophrenia patients and 47 age and sex-matched controls. Data was collected using a structured questionnaire. Serum was used for serological analysis of anti-T. gondii IgG and IgM antibodies through chemiluminescent immunoassay. Proportions and mean with standard deviations (SD) were used as descriptive measures and variables with p-values <0.05 were considered as statistically significant and independently associated with schizophrenia. RESULT: The mean ages of schizophrenia patients and controls were 29.64 ± 5.8 yrs and 30.98 ± 7.3 yrs, respectively. We found that 81.9% (77/94) of the study subjects had a positive anti-T. gondii IgG antibody. While the difference is statistically insignificant, schizophrenic patients have a marginally higher seroprevalence of toxoplasmosis than controls (87.2% vs 80.9%; p = 0.398). Schizophrenia cases who live in homes with soil floors have a significantly higher T. gondii infection as compared to those who live in homes with cement/ceramic floors (90.9% vs 33.3%; p = 0.004). Furthermore, there was a significantly lower T. gondii infection among schizophrenic cases who were taking antipsychotic medication for more than three yrs (79.3% vs 100.0%, p = 0.039). On the other hand, among all study subjects who have T. gondii infection, subjects who are addicted to khat and alcohol were about seven times more likely to develop schizophrenia (71.4% vs 47.7%, OR = 7.13, p = 0.024). CONCLUSION: Our data is not sufficient to show a significant positive correlation between T. gondii infection and schizophrenia. For study subjects with T. gondii infection, addiction to khat and alcohol is one of the risk factors for schizophrenia.

Norovirus-VLPs expressing pre-erythrocytic malaria antigens induce functional immunity against sporozoite infection.

Despite the development of prophylactic anti-malarial drugs and practices to prevent infection, malaria remains a health concern. Preclinical testing of novel malaria vaccine strategies achieved through rational antigen selection and novel particle-based delivery platforms is yielding encouraging results. One such platform, self-assembling virus-like particles (VLP) is safer than attenuated live viruses, and has been approved as a vaccination tool by the FDA. We explore the use of Norovirus sub-viral particles lacking the natural shell (S) domain forming the interior shell but that retain the protruding (P) structures of the native virus as a vaccine vector. Epitope selection and their surface display has the potential to focus antigen specific immune responses to crucial epitopes. Recombinant P-particles displaying epitopes from two malaria antigens, Plasmodium falciparum (Pf) CelTOS and Plasmodium falciparum (Pf) CSP, were evaluated for immunogenicity and their ability to confer protection in a murine challenge model. Immune responses induced in mice resulted either in sterile protection (displaying PfCelTOS epitopes) or in antibodies with functional activity against sporozoites (displaying PfCSP epitopes) in an in vitro liver-stage development assay (ILSDA). These results are encouraging and support further evaluation of this platform as a vaccine delivery system.

Exploring the Association Between Latent Toxoplasma gondii Infection and COVID-19 in Hospitalized Patients: First Registry-Based Study.

PURPOSE: This study aimed to determine the possible association between Toxoplasma gondii infection and COVID-19 outcomes among 133 patients with an RT-PCR-positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hospitalized at Imam Khomeini Hospital, Sari, Mazandaran Province, northern Iran, during August to November 2020. METHODS: A questionnaire was used to collect baseline data from the patients who were registered to the Iranian National Registry Center for Toxoplasmosis (INRCT). Also, blood samples were taken from each patient for detecting anti-T. gondii antibodies and T. gondii DNA using enzyme-linked immunosorbent assay (ELISA) and conventional-PCR methods, respectively. Variables related to the COVID-19 severity and outcomes were indicated based on multiple multinomial logistic regression models. RESULTS: Of 133 patients enrolled in the INRCT with COVID-19 through RT-PCR, 50 (37.59%), 52 (39.1%), and 31 (23%) suffered from mild, moderate, and severe COVID-19, respectively. 57.1% of the patients who died had severe COVID-19, while among those with other outcomes, only 18.60% had severe COVID-19 (P < 0.05). Anti-T. gondii IgG was detected in 109/133 (81.95%) patients, which was not statistically significant (P > 0.05). Among those with negative and positive anti-T. gondii IgG, 2 (8.30%) and 29 (26.60%) had severe COVID-19, respectively (P > 0.05). T. gondii DNA and anti-T. gondii IgM were not found in any of the patients. Moreover, all deaths occurred in those with moderate or severe COVID-19 and a positive anti-T. gondii IgG. CONCLUSION: To our knowledge, this is the first registry-based study concerning T. gondii infection among patients with COVID-19. Our data show the high rate of latent T. gondii infection among COVID-19 with different severity. However, there is no significant relationship between latent T. gondii infection and COVID-19 severity and outcomes. Thus, conducting multicenter studies in different geographic regions of the world could offer a better understanding of this relationship.

Monoclonal antibodies for malaria prevention.

Monoclonal antibodies are highly specific proteins that are cloned from a single B cell and bind to a single epitope on a pathogen. These laboratory-made molecules can serve as prophylactics or therapeutics for infectious diseases and have an impressive capacity to modulate the progression of disease, as demonstrated for the first time on a large scale during the COVID-19 pandemic. The high specificity and natural starting point of monoclonal antibodies afford an encouraging safety profile, yet the high cost of production remains a major limitation to their widespread use. While a monoclonal antibody approach to abrogating malaria infection is not yet available, the unique life cycle of the malaria parasite affords many opportunities for such proteins to act, and preliminary research into the efficacy of monoclonal antibodies in preventing malaria infection, disease, and transmission is encouraging. This review examines the current status and future outlook for monoclonal antibodies against malaria in the context of the complex life cycle and varied antigenic targets expressed in the human and mosquito hosts, and provides insight into the strengths and limitations of this approach to curtailing one of humanity's oldest and deadliest diseases.

Serum levels of C-reactive protein and ferritin in COVID-19 patients infected with Toxoplasma gondii.

During infection, T. gondii disseminates by the circulatory system and establishes chronic infection in several organs. Almost third of humans, immunosuppressed individuals such as HIV/AIDS patients, cancer patients, and organ transplant recipients are exposed to toxoplasmosis. Therefore, the study aimed to investigate the possibility that Toxoplasma infection could be a risk factor for COVID-19 patients and its possible correlation with C-reactive protein and ferritin. Overall 220 patients referred to the Al Furat General Hospital, Baghdad, Iraq were enrolled from 2020-2021. All serum samples were tested for T. gondii immunoglobulins (IgG and IgM) antibodies, C-reactive protein and ferritin levels. In patients with COVID-19, the results revealed a high positivity percentage for anti-Toxoplasma IgG. In COVID-19 patients infected with T. gondii, the C-reactive protein and ferritin levels were higher than the controls. The ferritin level was high in COVID-19 patients infected with toxoplasmosis compare with COVID-19 patient without toxoplasmosis in different gender and age while the level of CRP had no significant differences in COVID-19 patient with or without toxoplasmosis. These finding suggest that the incidental rate of toxoplasmosis could be considered as an indication to the high risk of COVID-19.

Coinfection between SARS-CoV-2 and vector-borne diseases in Luanda, Angola.

Co-epidemics happening simultaneously can generate a burden on healthcare systems. The co-occurrence of SARS-CoV-2 with vector-borne diseases (VBD), such as malaria and dengue in resource-limited settings represents an additional challenge to the healthcare systems. Herein, we assessed the coinfection rate between SARS-CoV-2 and VBD to highlight the need to carry out an accurate diagnosis and promote timely measures for these infections in Luanda, the capital city of Angola. This was a cross-sectional study conducted with 105 subjects tested for the SARS-CoV-2 and VBD with a rapid detection test in April 2021. The participants tested positive for SARS-CoV-2 (3.80%), malaria (13.3%), and dengue (27.6%). Low odds related to testing positivity to SARS-CoV-2 or VBD were observed in participants above or equal to 40 years (odds ratio [OR]: 0.60, p = 0.536), while higher odds were observed in male (OR: 1.44, p = 0.392) and urbanized areas (OR: 3.78, p = 0.223). The overall co-infection rate between SARS-CoV-2 and VBD was 11.4%. Our findings showed a coinfection between SARS-CoV-2 with malaria and dengue, which could indicate the need to integrate the screening for VBD in the SARS-CoV-2 testing algorithm and the adjustment of treatment protocols. Further studies are warranted to better elucidate the relationship between COVID-19 and VBD in Angola.

Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes.

BACKGROUND: The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria. An integral part of the severe malaria pathogenesis is rosetting, the adherence of parasite infected red blood cells (RBCs) to uninfected RBCs. Rosetting is influenced by the host's ABO blood group (Bg) and rosettes formed in BgA have previously been shown to be more resilient to disruption by heparin and shield the parasite derived surface antigens from antibodies. However, data on rosetting in weak BgA subgroups is scarce and based on investigations of relatively few donors. METHODS: An improved high-throughput flow cytometric assay was employed to investigate rosetting characteristics in an extensive panel of RBC donor samples of all four major ABO Bgs, as well as low BgA expressing samples. RESULTS: All non-O Bgs shield the parasite surface antigens from strain-specific antibodies towards P. falciparum erythrocyte membrane protein 1 (PfEMP1). A positive correlation between A-antigen levels on RBCs and rosette tightness was observed, protecting the rosettes from heparin- and antibody-mediated disruption. CONCLUSIONS: These results provide new insights into how the ABO Bg system affects the disease outcome and cautions against interpreting the results from the heterogeneous BgA phenotype as a single group in epidemiological and experimental studies.

Is COVID-19 associated with latent toxoplasmosis?

The present study aimed to evaluate the possible association between coronavirus disease 2019 (COVID-19) and latent Toxoplasma gondii infection in a group of patients and healthy individuals. Blood samples were obtained from 269 PCR-positive COVID-19 patients. The serum was separated and tested for the existence of anti-T. gondii antibodies (IgG) using a commercial enzyme-linked immunosorbent assay kit. The prevalence of latent toxoplasmosis between a subgroup of the patients (aged under 55 years old) and COVID-19 negative individuals was compared. Anti-T. gondii antibodies were found in 226/269 (84.0%) patients with COVID-19. Anti-Toxoplasma antibodies were detected in 72/91 (79.1%) cases and 96/123 (78.0%) COVID-19 negative individuals (odd ratio = 1.1; 95% confidence interval: 0.55-2.07, P = 0.85). The median and interquartile range (IQR) of the IgG titer were not statistically significant different between case (97.3 [31.0-133.5]) and control groups (34.4 [13.0-144.5]) (P = 0.10). These findings demonstrated that latent Toxoplasma infection is prevalent amongst the COVID-19 patients. It also did not find any significant association between chronic toxoplasmosis and COVID-19.

The link between Toxoplasma gondii infections and higher mortality in COVID-19 patients having schizophrenia.

A strong link between schizophrenia and a higher mortality rate from SARS-CoV-2 infections has been reported for schizophrenia patients, with a mortality odds ratio (OR) of 2.67 compared to normal patients, after adjustment of the OR for age, sex, race and extra risk factors. In addition, an extensive number of papers have reported a very strong link between schizophrenia and Toxoplasma gondii infections. A meta-analysis of 38 studies of links between schizophrenia and T. gondii antibody seroprevalence resulting from previous infections indicated that the likelihood of T. gondii infection in schizophrenia patients was 2.7 times higher than the general population. In other words, the meta-analysis indicated that schizophrenia patients had an odds ratio of 2.7 of T. gondii infection compared to the general population. This indicates that compared to the general population, schizophrenia patients have virtually the same odds ratio for having a T. gondii infection and for mortality from a COVID-19 infection. This suggests that T. gondii infections, directly or indirectly, have a relationship with higher mortality in COVID-19 patients having schizophrenia. This conclusion would also apply to the general population.

A Monoclonal Antibody for Malaria Prevention.

BACKGROUND: Additional interventions are needed to reduce the morbidity and mortality caused by malaria. METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum. Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria. Participants received CIS43LS subcutaneously or intravenously at one of three escalating dose levels. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS infusion. Additional participants were enrolled in Part B and received CIS43LS intravenously. To assess the protective efficacy of CIS43LS, some participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying P. falciparum sporozoites 4 to 36 weeks after administration of CIS43LS. RESULTS: A total of 25 participants received CIS43LS at a dose of 5 mg per kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 25 participants received a second dose (20 mg per kilogram regardless of initial dose). No safety concerns were identified. We observed dose-dependent increases in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 participants who received CIS43LS, as compared with 5 of 6 control participants who did not receive CIS43LS, had parasitemia according to polymerase-chain-reaction testing through 21 days after controlled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 µg per milliliter at the time of controlled human malaria infection. CONCLUSIONS: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.).

Screening of viral-vectored P. falciparum pre-erythrocytic candidate vaccine antigens using chimeric rodent parasites.

To screen for additional vaccine candidate antigens of Plasmodium pre-erythrocytic stages, fourteen P. falciparum proteins were selected based on expression in sporozoites or their role in establishment of hepatocyte infection. For preclinical evaluation of immunogenicity of these proteins in mice, chimeric P. berghei sporozoites were created that express the P. falciparum proteins in sporozoites as an additional copy gene under control of the uis4 gene promoter. All fourteen chimeric parasites produced sporozoites but sporozoites of eight lines failed to establish a liver infection, indicating a negative impact of these P. falciparum proteins on sporozoite infectivity. Immunogenicity of the other six proteins (SPELD, ETRAMP10.3, SIAP2, SPATR, HT, RPL3) was analyzed by immunization of inbred BALB/c and outbred CD-1 mice with viral-vectored (ChAd63 or ChAdOx1, MVA) vaccines, followed by challenge with chimeric sporozoites. Protective immunogenicity was determined by analyzing parasite liver load and prepatent period of blood stage infection after challenge. Of the six proteins only SPELD immunized mice showed partial protection. We discuss both the low protective immunogenicity of these proteins in the chimeric rodent malaria challenge model and the negative effect on P. berghei sporozoite infectivity of several P. falciparum proteins expressed in the chimeric sporozoites.

Immunoglobulin Y for Potential Diagnostic and Therapeutic Applications in Infectious Diseases.

Antiviral, antibacterial, and antiparasitic drugs and vaccines are essential to maintaining the health of humans and animals. Yet, their production can be slow and expensive, and efficacy lost once pathogens mount resistance. Chicken immunoglobulin Y (IgY) is a highly conserved homolog of human immunoglobulin G (IgG) that has shown benefits and a favorable safety profile, primarily in animal models of human infectious diseases. IgY is fast-acting, easy to produce, and low cost. IgY antibodies can readily be generated in large quantities with minimal environmental harm or infrastructure investment by using egg-laying hens. We summarize a variety of IgY uses, focusing on their potential for the detection, prevention, and treatment of human and animal infections.

RTS,S/AS01E malaria vaccine induces IgA responses against CSP and vaccine-unrelated antigens in African children in the phase 3 trial.

BACKGROUND: The evaluation of immune responses to RTS,S/AS01 has traditionally focused on immunoglobulin (Ig) G antibodies that are only moderately associated with protection. The role of other antibody isotypes that could also contribute to vaccine efficacy remains unclear. Here we investigated whether RTS,S/AS01E elicits antigen-specific serum IgA antibodies to the vaccine and other malaria antigens, and we explored their association with protection. METHODS: Ninety-five children (age 5-17 months old at first vaccination) from the RTS,S/AS01E phase 3 clinical trial who received 3 doses of RTS,S/AS01E or a comparator vaccine were selected for IgA quantification 1 month post primary immunization. Two sites with different malaria transmission intensities (MTI) and clinical malaria cases and controls, were included. Measurements of IgA against different constructs of the circumsporozoite protein (CSP) vaccine antigen and 16 vaccine-unrelated Plasmodium falciparum antigens were performed using a quantitative suspension array assay. RESULTS: RTS,S vaccination induced a 1.2 to 2-fold increase in levels of serum/plasma IgA antibodies to all CSP constructs, which was not observed upon immunization with a comparator vaccine. The IgA response against 13 out of 16 vaccine-unrelated P. falciparum antigens also increased after vaccination, and levels were higher in recipients of RTS,S than in comparators. IgA levels to malaria antigens before vaccination were more elevated in the high MTI than the low MTI site. No statistically significant association of IgA with protection was found in exploratory analyses. CONCLUSIONS: RTS,S/AS01E induces IgA responses in peripheral blood against CSP vaccine antigens and other P. falciparum vaccine-unrelated antigens, similar to what we previously showed for IgG responses. Collectively, data warrant further investigation of the potential contribution of vaccine-induced IgA responses to efficacy and any possible interplay, either synergistic or antagonistic, with protective IgG, as identifying mediators of protection by RTS,S/AS01E immunization is necessary for the design of improved second-generation vaccines. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT008666191.