Anti-RBD IgG antibodies from endemic coronaviruses do not protect against the acquisition of SARS-CoV-2 infection among exposed uninfected individuals.

Background: The Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases.

Enhanced Immunogenicity and Protective Effects against SARS-CoV-2 Following Immunization with a Recombinant RBD-IgG Chimeric Protein.

The unprecedented global impact caused by SARS-CoV-2 imposed huge health and economic challenges, highlighting the urgent need for safe and effective vaccines. The receptor-binding domain (RBD) of SARS-CoV-2 is the major target for neutralizing antibodies and for vaccine formulations. Nonetheless, the low immunogenicity of the RBD requires the use of alternative strategies to enhance its immunological properties.

Recombinant antigen delivery to dendritic cells as a way to improve vaccine design.

Dendritic cells are central to the development of immunity, as they are specialized in initiating antigen-specific immune responses. In this review, we briefly present the existing knowledge on dendritic cell biology and how their division in different dendritic cell subsets may impact the development of immune responses. In addition, we explore the use of chimeric monoclonal antibodies that bind to dendritic cell surface receptors, with an emphasis on the C-type lectin family of endocytic receptors, to deliver antigens directly to these cells.

Heterologous DNA Prime- Subunit Protein Boost with Chikungunya Virus E2 Induces Neutralizing Antibodies and Cellular-Mediated Immunity.

Chikungunya virus (CHIKV) has become a significant public health concern due to the increasing number of outbreaks worldwide and the associated comorbidities. Despite substantial efforts, there is no specific treatment or licensed vaccine against CHIKV to date. The E2 glycoprotein of CHIKV is a promising vaccine candidate as it is a major target of neutralizing antibodies during infection.

Targeting the P10 Peptide in Maturing Dendritic Cells via the DEC205 Receptor In Vivo: A New Therapeutic Strategy against Paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by , a thermally dimorphic fungus, which is the most frequent endemic systemic mycosis in many Latin American countries, where ~10 million people are believed to be infected. In Brazil, it is ranked as the tenth most common cause of death among chronic infectious diseases. Hence, vaccines are in development to combat this insidious pathogen.

Plasmodium vivax infection alters the peripheral immunoregulatory network of CD4 T follicular cells and B cells.

Regulatory and effector cell responses to Plasmodium vivax, the most common human malaria parasite outside Africa, remain understudied in naturally infected populations. Here, we describe peripheral CD4 T- and B-cell populations during and shortly after an uncomplicated P. vivax infection in 38 continuously exposed adult Amazonians.

Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells.

Introduction: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial () or insect cells (). The ZIKV-envelope glycoprotein (E) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The E is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes.

ZnO-Based Electrochemical Immunosensor to Assess Vaccine-Induced Antibody-Mediated Immunity against Wild-Type and Gamma SARS-CoV-2 Strains.

The evaluation of serological responses to COVID-19 is crucial for population-level surveillance, developing new vaccines, and evaluating the efficacy of different immunization programs. Research and development of point-of-care test technologies remain essential to improving immunity assessment, especially for SARS-CoV-2 variants that partially evade vaccine-induced immune responses. In this work, an impedimetric biosensor based on the immobilization of the recombinant trimeric wild-type spike protein (S protein) on zinc oxide nanorods (ZnONRs) was employed for serological evaluation.

Protein Arginylation Is Regulated during SARS-CoV-2 Infection.

Background: In 2019, the world witnessed the onset of an unprecedented pandemic. By February 2022, the infection by SARS-CoV-2 has already been responsible for the death of more than 5 million people worldwide. Recently, we and other groups discovered that SARS-CoV-2 infection induces ER stress and activation of the unfolded protein response (UPR) pathway.

Antibody cross-reactivity and evidence of susceptibility to emerging Flaviviruses in the dengue-endemic Brazilian Amazon.

Objectives: Several Flaviviruses can co-circulate. Pre-existing immunity to one virus can modulate the response to a heterologous virus; however, the serological cross-reaction between these emerging viruses in dengue virus (DENV)-endemic regions are poorly understood.

Methods: A cross-sectional study was performed among the residents of Manaus city in the state of Amazonas, Brazil.

Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape.

Introduction: Considering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information.

Methods: We used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals.

Results: We found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus.

The oldest unvaccinated Covid-19 survivors in South America.

Background: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated.

Results: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2.

STAT3 signaling modulates the immune response induced after antigen targeting to conventional type 1 dendritic cells through the DEC205 receptor.

Conventional dendritic cells (cDC) are a group of antigen-presenting cells specialized in priming T cell responses. In mice, splenic cDC are divided into conventional type 1 DC (cDC1) and conventional type 2 (cDC2). cDC1 are specialized to prime the Th1 CD4 T cell response, while cDC2 are mainly associated with the induction of follicular helper T cell responses to support germinal center formation.

Time-dependent contraction of the SARS-CoV-2-specific T-cell responses in convalescent individuals.

Background: Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation.

Reactivity of DENV-positive sera against recombinant envelope proteins produced in bacteria and eukaryotic cells.

Dengue is a mosquito-borne disease endemic in many tropical and subtropical countries. It is caused by the dengue virus (DENV) that can be classified into 4 different serotypes (DENV-1-4). Early diagnosis and management can reduce morbidity and mortality rates of severe forms of the disease, as well as decrease the risk of larger outbreaks.

ZIKV-envelope proteins induce specific humoral and cellular immunity in distinct mice strains.

Recent outbreaks of Zika virus (ZIKV) infection have highlighted the need for a better understanding of ZIKV-specific immune responses. The ZIKV envelope glycoprotein (E) is the most abundant protein on the virus surface and it is the main target of the protective immune response. E protein contains the central domain (EDI), a dimerization domain containing the fusion peptide (EDII), and a domain that binds to the cell surface receptor (EDIII).

Nano-multilamellar lipid vesicles promote the induction of SARS-CoV-2 immune responses by a protein-based vaccine formulation.

The development of safe and effective vaccine formulations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a hallmark in the history of vaccines. Here we report a COVID-19 subunit vaccine based on a SARS-CoV-2 Spike protein receptor binding domain (RBD) incorporated into nano-multilamellar vesicles (NMV) associated with monophosphoryl lipid A (MPLA). The results based on immunization of C57BL/6 mice demonstrated that recombinant antigen incorporation into NMVs improved antibody and T-cell responses without inducing toxic effects under both in vitro and in vivo conditions.

Validation of Serological Methods for COVID-19 and Retrospective Screening of Health Employees and Visitors to the São Paulo University Hospital, Brazil.

Reliable serological tests for the detection of SARS-CoV-2 antibodies among infected or vaccinated individuals are important for epidemiological and clinical studies. Low-cost approaches easily adaptable to high throughput screenings, such as Enzyme-Linked Immunosorbent Assays (ELISA) or electrochemiluminescence immunoassay (ECLIA), can be readily validated using different SARS-CoV-2 antigens. A total of 1,119 serum samples collected between March and July of 2020 from health employees and visitors to the University Hospital at the University of São Paulo were screened with the Elecsys Anti-SARS-CoV-2 immunoassay (Elecsys) (Roche Diagnostics) and three in-house ELISAs that are based on different antigens: the Nucleoprotein (N-ELISA), the Receptor Binding Domain (RBD-ELISA), and a portion of the S1 protein (ΔS1-ELISA).

Immunization with CSP and a RIG-I Agonist is Effective in Inducing a Functional and Protective Humoral Response Against .

Malaria is a major public health concern, as a highly effective human vaccine remains elusive. The efficacy of a subunit vaccine targeting the most abundant protein of the sporozoite surface, the circumsporozoite protein (CSP) has been hindered by difficulties in generating an effective humoral response in both quantity and quality. Using the rodent model we report here that immunization with CSP adjuvanted with 5'ppp-dsRNA, a RIG-I agonist, confers early and long-lasting sterile protection in mice against stringent sporozoite and mosquito bite challenges.

STAT6 signaling pathway controls germinal center responses promoted after antigen targeting to conventional type 2 dendritic cells.

Conventional dendritic cells (cDCs) are antigen-presenting cells specialized in naïve T cell priming. Mice splenic cDCs are classified as cDC1s and cDC2s, and their main functions have been elucidated in the last decade. While cDC1s are specialized in priming type 1 helper T cells (T1) and in cross presentation, cDC2s prime T follicular helper (T) cells that stimulate germinal center (GC) formation, plasma cell differentiation and antibody production.

Silent circulation of Chikungunya virus among pregnant women and newborns in the Western Brazilian Amazon before the first outbreak of chikungunya fever.

The prevalence of immunity to Chikungunya virus (CHIKV) in pregnant women and newborns in the Western Brazilian Amazon was assessed at a time when previous studies did not report chikungunya fever in the area. In 435 asymptomatic pregnant women and 642 healthy unrelated newborns, the presence of IgM and IgG antibodies to CHIKV were determined by a commercial ELISA. All participants were negative to IgM anti-CHIKV.

Reduced T Cell and Antibody Responses to Inactivated Coronavirus Vaccine Among Individuals Above 55 Years Old.

CoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals.

Recurrence of COVID-19 associated with reduced T-cell responses in a monozygotic twin pair.

Recurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence.