Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation.

We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (São Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.

Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline.

BACKGROUND: The live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine. METHODS: Neutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees. RESULTS AND DISCUSSION: The results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10). CONCLUSIONS: The analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine.

HIV cure: global overview of bNAbs' patents and related scientific publications.

INTRODUCTION: This article provides a global overview of patent deposits for broadly neutralizing antibodies (bNAbs), which have emerged as a key strategy for HIV cure and future HIV vaccines. Scientific and technological barriers to the discovery of an effective HIV vaccine in the last 40 years have raised concerns on the potential for relevant advances in this area. Nevertheless, recent breakthrough studies have identified novel immune pathways for new innovative HIV vaccine and HIV cure strategies. AREAS COVERED: In our patent study, we have identified in a global scale, in the last decade, a sharp increase in the number of bNAbs' patent deposits related to HIV prevention and treatment strategies, reaching 90 bNAbs in 2017, protected by 184 different patent deposits. Refining our patent search to the different stages of bNAbs' development has also allowed us to identify 12 of them already at clinical stage of research (VRC01, 10E8, 3BNC117, 10-1074, 2G12, 2F5, KD-247, 4E10, PG9, PGDM1400, PGT121, and VRC07). We describe these recent breakthroughs and discuss the prospects and limitations of these novel strategies. EXPERT OPINION: Our results indicate the intellectual property outcomes of a scientific revolution in this field, expressing innovative modifications in antibodies to increase their potency and half-life, which have resulted in extremely potent antibodies that could provide novel preventive and therapeutic HIV strategies.

Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation

We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (São Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.

Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B.

The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang) were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70%) met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566), children 1 to 10 years old (484), adolescents from 11 to 19 years (740), adults from 20 to 30 years (568), and adults from 31 to 40 years (396). Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults) or 0, 1, and 7 months (children). Vaccine dose was intramuscular 10 microg (infants, children, and adolescents) or 20 microg (adults). Percent seroprotection (assumed when anti-HBs titers were > 10 mIU/ml) and geometric mean titer (mIU/ml) were: newborn infants, 93.7% and 351.1 (Butang) and 97.5% and 1530.6 (Engerix B); children, 100% and 3600.0 (Butang) and 97.7% and 2753.1 (Engerix B); adolescents, 95.1% and 746.3 (Butang) and 96% and 1284.3 (Engerix B); adults 20-30 years old, 91.8% and 453.5 (Butang) and 95.5% and 1369.0 (Engerix B); and adults 31-40 years old, 79.8% and 122.7 (Butang) and 92.4% and 686.2 (Engerix B). There were no severe adverse events following either vaccine. The study concluded that Butang was equivalent to Engerix B in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.

Desenvolvimento tecnológico: elo deficiente na inovaçäo tecnológica de vacinas no Brasil / Technological development: a weak link in vaccine innovation in Brazil

Apresenta-se neste trabalho a situaçäo da vacinaçäo, produçäo e desenvolvimento tecnológico de vacinas no mundo e no Brasil; também säo feitas algumas reflexöes sobre a complexidade da inovaçäo tecnológica de vacinas e as diversas etapas do processo de desenvolvimento tecnológico requeridas para esse completo desenvolvimento. Descrevem-se várias etapas envolvidas, com análise dos parâmetros e fatores integrantes em cada etapa, os requisitos técnicos de instalaçöes e equipamentos, as normas de boas práticas de fabricaçäo(BPF_), a necessidade organizacional, de infra-estrutura e de gestäo, o longo período e o alto custo demandados para essa atividade.

Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang®) were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B® was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70 percent) met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566), children 1 to 10 years old (484), adolescents from 11 to 19 years (740), adults from 20 to 30 years (568), and adults from 31 to 40 years (396). Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults) or 0, 1, and 7 months (children). Vaccine dose was intramuscular 10 æg (infants, children, and adolescents) or 20 æg (adults). Percent seroprotection (assumed when anti-HBs titers were > 10mIU/ml) and geometric mean titer (mIU/ml) were: newborn infants, 93.7 percent and 351.1 (Butang®) and 97.5 percent and 1530.6 (Engerix B®); children, 100 percent and 3600.0 (Butang®) and 97.7 percent and 2753.1 (Engerix B®); adolescents, 95.1 percent and 746.3 (Butang®) and 96 percent and 1284.3 (Engerix B®); adults 20-30 years old, 91.8 percent and 453.5 (Butang®) and 95.5 percent and 1369.0 (Engerix B®); and adults 31-40 years old, 79.8 percent and 122.7 (Butang®) and 92.4 percent and 686.2 (Engerix B®). There were no severe adverse events following either vaccine. The study concluded that Butang® was equivalent to Engerix B® in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.

História da Pediatria brasileira: coletânea de textos e depoimentos / The history of the Brazilian pediatrics: collection of texts and statements

Mostra a trajetória da construção da Pediatria brasileira e da Sociedade Brasileira de Pediatria, através de textos e depoimentos.