Plasmodium falciparum merozoite surface protein 3 as a vaccine candidate: a brief review.

Despite the many efforts of researchers around the world, there is currently no effective vaccine for malaria. Numerous studies have been developed to find vaccine antigens that are immunogenic and safe. Among antigen candidates, Plasmodium falciparum merozoite surface protein 3 (MSP3) has stood out in a number of these studies for its ability to induce a consistent and protective immune response, also being safe for use in humans. This review presents the main studies that explored MSP3 as a vaccine candidate over the last few decades. MSP3 formulations were tested in animals and humans and the most advanced candidate formulations are MSP3-LSP, a combination of MSP3 and LSP1, and GMZ2 (a vaccine based on the recombinant protein fusion GLURP and MSP3) which is currently being tested in phase II clinical studies. This brief review highlights the history and the main formulations of MSP3-based vaccines approaches against P. falciparum .

Circumsporozoite Surface Protein-based malaria vaccines: a review.

Malaria represents a serious public health problem, presenting with high rates of incidence, morbidity and mortality in tropical and subtropical regions of the world. According to the World Health Organization, in 2018 there were 228 million cases and 405 thousand deaths caused by this disease in the world, affecting mainly children and pregnant women in Africa. Despite the programs carried out to control this disease, drug resistance and invertebrate vector resistance to insecticides have generated difficulties. An efficient vaccine against malaria would be a strategy with a high impact on the eradication and control of this disease. Researches aimed at developing vaccines have focused on antigens of high importance for the survival of the parasite such as the Circumsporozoite Surface Protein, involved in the pre-erythrocytic cycle during parasites invasion in hepatocytes. Currently, RTS'S is the most promising vaccine for malaria and was constructed using CSP; its performance was evaluated using two types of adjuvants: AS01 and AS02. The purpose of this review was to provide a bibliographic survey of historical researches that led to the development of RTS'S and its performance analysis over the decade. The search for new adjuvants to be associated with this antigen seems to be a way to obtain higher percentages of protection for a future malaria vaccine.

HTLV-2 infection in Manaus, Brazil: first description of HTLV-2c subtype in an urban area of the Western Amazon region.

INTRODUCTION: We investigated the prevalence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) infection in patients with hematological diseases from the western Amazon region of Brazil. METHODS: Samples from 306 patients were submitted for the molecular diagnosis of HTLV-1/2 infection by real time PCR (qPCR), with amplification, sequencing, and phylogenetic analysis of the long terminal repeat (LTR) region. RESULTS: A 29-year-old male carrier of sickle cell anemia with a history of multiple blood transfusions was diagnosed with the HTLV-2c subtype. CONCLUSIONS: This study describes the first known occurrence of HTLV-2c in the urban area of Brazil's western Amazon region.

Chicken eggs as a surveillance tool for malaria and leishmaniasis vector presence.

INTRODUCTION: Malaria and leishmaniases are transmitted by vectors during blood-feeding. Vector-infected animals develop antibodies against the vector's saliva. This study evaluated IgY antibody detection in the chicken eggs exposed to bites from Migonemyia migonei, Lutzomyia longipalpis and Anopheles aquasalis. METHODS: We used ELISA to quantify the antibody levels in the sera and exposed chicken eggs. RESULTS: High IgY levels were observed following immunization; furthermore, higher reactivity was observed in the eggs and species-specific immune response was observed post final immunization. CONCLUSIONS: Chicken eggs can be used as sentinels to surveil vector saliva antibodies.

Plasmodium falciparum merozoite surface protein 3 as a vaccine candidate: a brief review

ABSTRACT Despite the many efforts of researchers around the world, there is currently no effective vaccine for malaria. Numerous studies have been developed to find vaccine antigens that are immunogenic and safe. Among antigen candidates, Plasmodium falciparum merozoite surface protein 3 (MSP3) has stood out in a number of these studies for its ability to induce a consistent and protective immune response, also being safe for use in humans. This review presents the main studies that explored MSP3 as a vaccine candidate over the last few decades. MSP3 formulations were tested in animals and humans and the most advanced candidate formulations are MSP3-LSP, a combination of MSP3 and LSP1, and GMZ2 (a vaccine based on the recombinant protein fusion GLURP and MSP3) which is currently being tested in phase II clinical studies. This brief review highlights the history and the main formulations of MSP3-based vaccines approaches against P. falciparum .

HTLV-2 infection in Manaus, Brazil: first description of HTLV-2c subtype in an urban area of the Western Amazon region

Abstract INTRODUCTION: We investigated the prevalence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) infection in patients with hematological diseases from the western Amazon region of Brazil. METHODS: Samples from 306 patients were submitted for the molecular diagnosis of HTLV-1/2 infection by real time PCR (qPCR), with amplification, sequencing, and phylogenetic analysis of the long terminal repeat (LTR) region. RESULTS: A 29-year-old male carrier of sickle cell anemia with a history of multiple blood transfusions was diagnosed with the HTLV-2c subtype. CONCLUSIONS: This study describes the first known occurrence of HTLV-2c in the urban area of Brazil's western Amazon region.

Chicken eggs as a surveillance tool for malaria and leishmaniasis vector presence

Abstract INTRODUCTION: Malaria and leishmaniases are transmitted by vectors during blood-feeding. Vector-infected animals develop antibodies against the vector's saliva. This study evaluated IgY antibody detection in the chicken eggs exposed to bites from Migonemyia migonei, Lutzomyia longipalpis and Anopheles aquasalis. METHODS: We used ELISA to quantify the antibody levels in the sera and exposed chicken eggs. RESULTS: High IgY levels were observed following immunization; furthermore, higher reactivity was observed in the eggs and species-specific immune response was observed post final immunization. CONCLUSIONS: Chicken eggs can be used as sentinels to surveil vector saliva antibodies.

Avaliação da resposta imune humoral produzida contra a proteína do circunsporozoíto (CSP) de Plasmodium falciparum associados à esporos de Bacillus subtilis

Atualmente, ainda não existe vacina para malária com capacidade de gerar uma proteção com alta eficácia, sendo as formulações que contêm a proteína de superfície de circunsporozoíto (PfCSP) as mais avançadas nos estudos em humanos. Uma etapa importante no desenvolvimento de uma vacina, além da identificação do antígeno, é avaliar como este será apresentado, bem como o efeito imunoestimulatório dos componentes da formulação (imunoestimulantes). Os esporos de Bacillus subtilis têm sido avaliados há duas décadas como partículas vacinais adjuvantes, as quais promovem a elevação da resposta humoral após a coadministração com antígenos tanto acoplados ou integrados à sua superfície. Logo, somando as características imunoestimulantes, probióticas e de alta resistência dos esporos com a grande capacidade de estimular uma resposta humoral protetora da PfCSP, este trabalho buscou investigar em modelo murino a possível utilização deste método como uma nova formulação de adjuvante para uma vacina contra malária. Para tanto, duas abordagens de apresentação foram testadas: acoplando a PfCSP recombinante (rPfCSP, produzida em Escherichia coli) na superfície dos esporos e recombinando o B. subtilis de modo a expressar o antígeno na superfície de seus esporos. Com as ferramentas produzidas, camundongos Balb/c foram imunizados via intranasal, sendo a resposta imune humoral (IgG total e subclasses) acompanhada por ELISA indireto. Os resultados obtidos neste trabalho demonstraram que a proteína rPfCSP foi produzida com êxito no sistema de expressão usando E. coli como hospedeiro, no qual estava presente porção solúvel do lisado bacteriano. As imunizações por via intranasal utilizando a rPfCSP acoplada aos esporos revelaram que estes podem estimular uma maior produção de anticorpos, mais rápida e por um período mais longo contra o antígeno rPfCSP quando comparada ao grupo estimulado apenas com a proteína recombinante. Além disso, foi observada uma resposta imune de perfil balanceado Th1/Th2 após análise do perfil de produção das subclasses. A recombinação da proteína PfCSP em B. subtilis foi obtida com sucesso, esta foi expressa na superfície dos esporos pelo endereçamento obtido com fusão à proteína C de revestimento do esporo( CotC), no qual não foram observadas clivagens do antígeno-alvo nos imunoensaios realizados, indicandoque esta não sofreu ação das proteases ainda presentes no hospedeiro utilizado. Os esporos de B. subtilis recombinados com PfCSP foram capazes de induzir uma resposta imune por via intranasal com níveis de IgG elevados que se mantiveram circulantes por 150 dias, apresentando um perfil de resposta imune predominante Th1. Este foi o primeiro estudo que buscou avaliar o potencial uso de esporos de B. subtilis como adjuvante de um antígeno candidato vacinal para malária. Os resultados promissores aqui obtidos podem reacender o interesse no potencial uso da via de mucosa, como forma não invasiva para obtenção de proteção contra a esta doença