André Vale | Universidade Federal do Rio de Janeiro (UFRJ) (original) (raw)

Papers by André Vale

Frontiers in Immunology

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an eff... more The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid [Poly(I:C)] adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2in vitroby neutralization assay, after two or three immunizations. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+a...

Frontiers in Cellular and Infection Microbiology, 2019

Journal of Experimental Medicine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in ... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in part because of the emergence of variants of concern that evade neutralization by antibodies elicited by prior infection or vaccination. Here we report on human neutralizing antibody and memory responses to the Gamma variant in a cohort of hospitalized individuals. Plasma from infected individuals potently neutralized viruses pseudotyped with Gamma SARS-CoV-2 spike protein, but neutralizing activity against Wuhan-Hu-1-1, Beta, Delta, or Omicron was significantly lower. Monoclonal antibodies from memory B cells also neutralized Gamma and Beta pseudoviruses more effectively than Wuhan-Hu-1. 69% and 34% of Gamma-neutralizing antibodies failed to neutralize Delta or Wuhan-Hu-1. Although Class 1 and 2 antibodies dominate the response to Wuhan-Hu-1 or Beta, 54% of antibodies elicited by Gamma infection recognized Class 3 epitopes. The results have implications for variant-specific vaccines and...

Immunological Reviews, Jun 26, 2018

Although at first glance the diversity of the immunoglobulin repertoire appears random, there are... more Although at first glance the diversity of the immunoglobulin repertoire appears random, there are a number of mechanisms that act to constrain diversity. For example, key mechanisms controlling the diversity of the third complementarity determining region of the immunoglobulin heavy chain (CDR-H3) include natural selection of germline diversity (D H) gene segment sequence and somatic selection upon passage through successive B-cell developmental checkpoints. To test the role of D H gene segment sequence, we generated a panel of mice limited to the use of a single germline or frameshifted D H gene segment. Specific individual amino acids within core D H gene segment sequence heavily influenced the absolute numbers of developing and mature Bcell subsets, antibody production, epitope recognition, protection against pathogen challenge, and susceptibility to the production of autoreactive antibodies. At the tip of the antigen-binding loop (PDB position 101) in CDR-H3, both natural (germline) and somatic selection favored tyrosine while disfavoring the presence of hydrophobic amino acids. Enrichment for arginine in CDR-H3 appeared to broaden recognition of epitopes of varying hydrophobicity, but led to diminished binding intensity and an increased likelihood of generating potentially pathogenic dsDNA-binding autoreactive antibodies. The phenotype of altering the sequence of the D H was recessive for T-independent antibody production, but dominant for T-cell-dependent responses. Our work suggests that the antibody repertoire is structured, with the sequence of individual D H selected by evolution to preferentially generate an apparently preferred category of antigenbinding sites. The result of this structured approach appears to be a repertoire that has been adapted, or optimized, to produce protective antibodies for a wide range of pathogen epitopes while reducing the likelihood of generating autoreactive specificities.

Journal of Immunology, May 1, 2020

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an eff... more The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid (Poly(I:C)) adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2in vitroby neutralization assay, after one or two boosts. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+and CD8+T ...

Frontiers in Medicine, 2021

Background: Convalescent plasma is a potential therapeutic option for critically ill patients wit... more Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19.Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan–Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed.Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48–68), disease duration was 10 days (IQR 6–13), and 86% were mechanically venti...

SSRN Electronic Journal, 2020

Background: Large-scale epidemiological studies of seroprevalence of antibodies against SARS-CoV-... more Background: Large-scale epidemiological studies of seroprevalence of antibodies against SARS-CoV-2 often rely on point-of-care tests that provide immediate results to participants. Yet, little is known on how long rapid tests remain positive after the COVID-19 episode, or how much variability exists across different brands and even among batches of the same test. Methods: In November 2020, we assessed the sensitivity of three tests applied to 133 individuals with a previous positive PCR result between April and October. All subjects provided finger prick blood samples for two batches (A and B) of the Wondfo lateral-flow IgG/IgM test, and dried blood spot samples for the S-UFRJ ELISA test. Results: Overall sensitivity levels were 92.5% (95% CI 86.6−96.3), 63.2% (95% CI 54.4−71.4) and 33.8% (95% CI 25.9−42.5) for the S-UFRJ test, Wondfo A and Wondfo B tests, respectively. There was no evidence of a decline in the positivity of S-UFRJ with time since the diagnosis, but the two Wondfo batches showed sharp reductions to as low as 41.9% and 19.4%,

Scientific Reports, 2019

CD43 (leukosialin) is a large sialoglycoprotein abundantly expressed on the surface of most cells... more CD43 (leukosialin) is a large sialoglycoprotein abundantly expressed on the surface of most cells from the hematopoietic lineage. CD43 is directly involved in the contact between cells participating in a series of events such as signaling, adherence and host parasite interactions. In this study we examined the role of CD43 in the immune response againstTrypanosoma cruzi, the protozoan parasite that causes Chagas’ disease, a potential life-threatening illness endemic in 21 Latin American countries according to the WHO. The acute stage of infection is marked by intense parasitemia and cardiac tissue parasitism, resulting in the recruitment of inflammatory cells and acute damage to the heart tissue. We show here thatCD43−/−mice were more resistant to infection due to increased cytotoxicity of antigen specific CD8+ T cells and reduced inflammatory infiltration in the cardiac tissue, both contributing to lower cardiomyocyte damage. In addition, we demonstrate that the induction of acute ...

Annals of the New York Academy of Sciences, 2015

Because of N addition and variation in the site of VDJ joining, the third complementarity‐determi... more Because of N addition and variation in the site of VDJ joining, the third complementarity‐determining region of the heavy chain (CDR‐H3) is the most diverse component of the initial immunoglobulin antigen‐binding site repertoire. A large component of the peritoneal cavity B‐1 cell component is the product of fetal and perinatal B cell production. The CDR‐H3 repertoire is thus depleted of N addition, which increases dependency on germ‐line sequence. Cross‐species comparisons have shown that DH gene sequence demonstrates conservation of amino acid preferences by reading frame. Preference for reading frame 1, which is enriched for tyrosine and glycine, is created both by rearrangement patterns and by pre‐BCR and BCR selection. In previous studies, we have assessed the role of conserved DH sequence by examining peritoneal cavity B‐1 cell numbers and antibody production in BALB/c mice with altered DH loci. Here, we review our finding that changes in the constraints normally imposed by ge...

Parasites & Vectors, 2015

Background: Leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania proto... more Background: Leishmaniasis is a neglected vector-borne tropical disease caused by Leishmania protozoa that are transmitted to mammalian hosts by infected sand flies. Infection is associated with distinct clinical manifestations that include cutaneous, mucocutaneous and visceral lesions. Visceral leishmaniasis (VL) is the most severe form of the disease and is considered second in terms of mortality and fourth in terms of morbidity among tropical diseases. IFN-γ-producing T cells are involved in protection against the disease. Methods: CD43 +/+ and CD43-/mice on a C57BL/6 background were intravenously injected with 5 × 10 7 amastigotes of Leishmania (L.) infantum chagasi, and 30 days after infection the clinical signs of disease were examined; the splenocytes were isolated and assayed for cytokine production; and the livers were removed for phenotypic analysis of T cell subsets by flow cytometry. Results: We report that mice lacking CD43 display increased susceptibility to infection by Leishmania (L.) infantum chagasi, with higher parasite burdens than wild-type mice. The increased susceptibility of CD43 −/− mice were associated with a weakened delayed hypersensitivity response and reduced levels of IgG2a antibodies to leishmania antigens. We further showed that expression of CD43 defines a major intrahepatic CD4 + and CD8 + T cell subsets with pro-inflammatory phenotypes and leads to increased levels of IFN-γ secretion by activated splenocytes. Conclusions: Our findings point to a role of CD43 in the development of host resistance to visceral leishmaniasis.

International Immunology, 2010

Mammalian TOR is a key component of a signaling pathway that integrates inputs from nutrients and... more Mammalian TOR is a key component of a signaling pathway that integrates inputs from nutrients and growth factors to regulate cell growth and metabolism. Because disruption of the mouse mTOR gene leads to early postimplantation lethality, we generated a mouse knockdown model, which recapitulates mTOR inhibition by drugs. Neo insertion interrupts transcription, leading to a 70% reduction in mTOR expression. The homozygous knockdown mice exhibit reductions in body, organ and cell size. Spleens are disproportionately smaller relative to overall body weight than other organs. Cell proliferation was decreased in splenic B cells. LPS-induced proliferation in B cells was reduced. Splenic B cell populations had more mature cells (IgDhi CD21+ IgM-), with fewer transitional cells (IgDhiIgMhi), and markedly reduced marginal zone B cells (IgDlowCD21hiIgMhi). Phosphorylation of AKT was increased in B cells after LPS stimulation, similar to what has been reported in PBMCs receiving long-term rapamycin treatment. B220+ B cells were decreased in bone marrow and alterations were seen in pre-B cell maturation. Antibody production, germinal center formation and class switch recombination were compromised in the mTOR knockdown mice. These data suggest that mTOR plays a role in the maturation and differentiation of B cell lineages, as well as in the regulation of immune responses.

International immunology, Jan 6, 2018

The incidence of allergic diseases, which increased to epidemic proportions in developed countrie... more The incidence of allergic diseases, which increased to epidemic proportions in developed countries over the last few decades, has been correlated with altered gut microbiota colonization. Although probiotics may play a critical role on the restoration of gut homeostasis, its efficiency on the control of allergy is controversial. Here we aimed to investigate the effects of probiotic treatment initiated at neonatal or adult ages on the suppression of experimental ovalbumin-induced asthma. Neonatal or adult mice were orally treated with probiotic bacteria and subjected to ovalbumin-induced allergy. Asthma-like symptoms, microbiota composition and frequencies of the total CD4+ and CD4+Foxp3+ regulatory T (Treg) cells were evaluated in both groups. Probiotic administration to neonates, but not to adults, was necessary and sufficient for the absolute prevention of experimental allergen-induced sensitization. The neonatally-acquired tolerance, transferrable to probiotic-untreated adult rec...

Vaccines

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the ... more Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4+ T-cells in mice. Altogether, those data ind...

We describe a cost-effective, scalable technology to produce SARS-COV-2 spike (S) protein based o... more We describe a cost-effective, scalable technology to produce SARS-COV-2 spike (S) protein based on stable expression in HEK293 cells, and its use to develop a highly specific and sensitive ELISA test. The assay allows early detection of anti-S IgG seroconversion and endpoint titers correlate with virus neutralization. The lowcost S-antigen production, together with sample collection by finger prick and dried blood spots, allowed the development of a half-dollar test that fits the urgent need for large-scale serological surveillance in low-income countries.

‡ These authors contributed equally to this work.

PLOS ONE, 2015

Frequency of peritoneal cavity B-1a cells expressing dsDNA-binding BCR by genotype. PerC... more Frequency of peritoneal cavity B-1a cells expressing dsDNA-binding BCR by genotype. PerC B-1a cells were sorted and cultured under polyclonal stimulation for IgM secretion. The frequency of B-1a cells secreting IgM anti-dsDNA in vitro was estimated by LDA. A) Histogram bars show the frequency, calculated by the Poisson distribution, of culture supernatants containing IgM binding to dsDNA. B) O.D. values of individual culture with variable numbers of B-1a cells. C) Evaluation of anti-dsDNA binding of culture supernatants containing 10,000 B-1a cells and similar amount of total IgM per culture. D) Binding to non-related antigen (phosphorylcholine—PC) using the same culture supernatants to control for the specificity of the assay. Significantly different from WT: *, P ≤ 0.05; **, P ≤ 0.01.</p

SSRN Electronic Journal, 2020

Background: Accurate serological tests are essential tools to allow adequate monitoring and contr... more Background: Accurate serological tests are essential tools to allow adequate monitoring and control of COVID-19 spread. Production of a low-cost and high-quality recombinant viral antigen can enable the development of reliable and affordable serological assays, which are urgently needed to facilitate epidemiological surveillance studies in low-income economies. Methods: Trimeric SARS-COV-2 spike (S) protein was produced in serum-free, suspension-adapted HEK293 cells. Highly purified S protein was used to develop an ELISA, named S-UFRJ test. It was standardized to work with different types of samples: (i) plasma or serum from venous blood samples; (ii) dried blood spots (DBS) from blood drops collected by finger prick. Findings: We developed a cost-effective, scalable technology to produce S protein based on its stable expression in HEK293 cells. The S-UFRJ ELISA displayed 98.4% specificity and sensitivity above 90% already 10 days after symptoms onset, allowing early detection of an...

Cite this article: Vale AM, Nobrega A, Schroeder HW Jr (2013) Linkage of Natural Antibody Immunol... more Cite this article: Vale AM, Nobrega A, Schroeder HW Jr (2013) Linkage of Natural Antibody Immunologic Homeostasis to Anticipatory Protection against a Common Pathogen Requires Natural Selection of Immunoglobulin Diversity Gene Segment Sequence. J Immunol Clin Res 1: 1005. *Corresponding author Harry W. Schroeder Jr., Departments of Medicine, Microbiology and Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA, Tel: 205-9341522; Fax: 205-975-6352; E-mail: hwsj@uab.edu

PLOS ONE, 2015

A) Germline sequences of DH genes and translat... more A) Germline sequences of DH genes and translation in reading frames (RF) 1–3. DFL16.1 RF1 encodes mostly neutral amino acids (green) while iD RF1 encodes mostly charged amino acids (red). In both genes, RF2 encodes hydrophobic amino acids (blue) and RF3 contains stop codons (*). B) Percentage CDR-H3 loop sequences containing arginines in Kabat position 95–98, 100–100a, or both. C) Distribution of arginines per CDR-H3 sequence in 8 week bone marrow immature B cells as a function of DH content and the presence or absence of TdT. The sequences from TdT-sufficient ΔD-DFL, WT and ΔD-iD mice, and TdT deficient WT mice were previously reported, but reanalyzed for this work [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118171#pone.0118171.ref018" target="_blank">18</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118171#pone.0118171.ref034" target="_blank">34</a>]. The inner circle contains the total number of sequences examined.</p

Frontiers in Immunology

Frontiers in Cellular and Infection Microbiology, 2019

Journal of Experimental Medicine

Immunological Reviews, Jun 26, 2018

Journal of Immunology, May 1, 2020

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an eff... more The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid (Poly(I:C)) adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2in vitroby neutralization assay, after one or two boosts. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+and CD8+T ...

Frontiers in Medicine, 2021

SSRN Electronic Journal, 2020

Scientific Reports, 2019

Annals of the New York Academy of Sciences, 2015

Parasites & Vectors, 2015

International Immunology, 2010

International immunology, Jan 6, 2018

Vaccines

‡ These authors contributed equally to this work.

PLOS ONE, 2015

SSRN Electronic Journal, 2020

PLOS ONE, 2015