Safety and immunogenicity of different 17DD yellow fever vaccines in golden-headed tamarins (Leontopithecus chrysomelas): Inhibition of viremia and RNAemia after homologous live-attenuated vaccination.

Yellow fever (YF) is a viral disease that affects both humans and non-human primates (NHPs). Neotropical monkeys are more severely stricken by YF and the impact of the disease can be devastating to the endangered golden-headed lion tamarins (GHLTs, Leontopithecus chrysomelas). Susceptible GHLTs were immunized with the commercial Brazilian YF 17DD live attenuated vaccine or two other experimental non-replicating YF vaccines: a purified whole-virus, b-propiolactone-inactivated vaccine and a plant-derived recombinant subunit vaccine.

Evaluation of Two Adjuvant Formulations for an Inactivated Yellow Fever 17DD Vaccine Candidate in Mice.

The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly stimulate the innate response to target protective immune responses.

Neotropical Sylvatic Mosquitoes and Are Not Competent to Transmit 17DD Attenuated Yellow Fever Virus from Vaccinated Viremic New World Non-Human Primates.

Beside humans, thousands of non-human primates (NHPs) died during the recent outbreak caused by the yellow fever virus (YFV) in Brazil. Vaccination of NHPs against YFV with the YF 17DD attenuated virus has emerged as a public health strategy, as it would reduce sylvatic transmission while also preserving endangered susceptible species. The hypothesis of establishing an uncontrolled transmission of this attenuated virus in nature was raised.

Safety and immunogenicity of 17DD attenuated yellow fever vaccine in howler monkeys (Alouatta spp.).

Background: Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP).

Vaccines for neglected and emerging diseases in Brazil by 2030: the "valley of death" and opportunities for RD&I in Vaccinology 4.0.

We examine the implications of the very low competitiveness of the Brazilian vaccine RD&I system, which precludes the development of all the important vaccines required by the National Immunization Program (NIP), severely impacting the healthcare of the population. In a country dramatically affected by COVID-19 pandemic and by an exponential increase in emerging and neglected diseases, particularly the poor, these RD&I constraints for vaccines become crucial governance issues. Such constraints are aggravated by a global scenario of limited commercial interest from multinational companies in vaccines for neglected and emerging diseases, which are falling into a "valley of death," with only two vaccines produced in a pipeline of 240 vaccines.

Regulatory evolution and challenges from the perspective of public laboratiories vaccine producers in Brazil.

The regulation of biological products has evolved rapidly in recent years due to quality issues impacting people's lives and the advent of new technologies, with constant changes in regulations that dictate how a product is registered, produced, and monitored. In the case of vaccines, the responsibility of regulators and manufacturers in guaranteeing quality, safety, and efficacy is even more critical, since vaccines are mostly used in children and healthy patients. In this scenario, manufacturers need to create strategies to keep their products and installations adequate and up-to-date with a fully operational quality system.

Short-Lived Immunity After 17DD Yellow Fever Single Dose Indicates That Booster Vaccination May Be Required to Guarantee Protective Immunity in Children.

The Yellow Fever (YF) vaccination is recommended for people living in endemic areas and represents the most effective strategy to reduce the risk of infection. Previous studies have warned that booster regimens should be considered to guarantee the long-term persistence of 17DD-YF-specific memory components in adults living in areas with YF-virus circulation. Considering the lower seroconversion rates observed in children (9-12 months of age) as compared to adults, this study was designed in order to access the duration of immunity in single-dose vaccinated children in a 10-years cross-sectional time-span.

Sanger-based sequencing technology for yellow fever vaccine genetic quality control.

Yellow Fever (YF) is an acute viral hemorrhagic disease prevalent mainly in Africa and Americas, with 20-60% fatality rate in severe forms. Currently, antiviral drugs for the infection are not available, reinforcing the importance of vaccination in resident populations and travelers. Manufactured in 7 different countries, the YF vaccine was first created in 1937 and two substrains are used for production, 17DD and 17D-204.

Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination.

In this investigation, machine-enhanced techniques were applied to bring about scientific insights to identify a minimum set of phenotypic/functional memory-related biomarkers for post-vaccination follow-up upon yellow fever (YF) vaccination. For this purpose, memory status of circulating T-cells (Naïve/early-effector/Central-Memory/Effector-Memory) and B-cells (Naïve/non-Classical-Memory/Classical-Memory) along with the cytokine profile (IFN/TNF/IL-5/IL-10) were monitored before-NV(day0) and at distinct time-points after 17DD-YF primary vaccination-PV(day30-45); PV(year1-9) and PV(year10-11). A set of biomarkers (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) were observed in PV(day30-45), but not in NV(day0), with most of them still observed in PV(year1-9).

Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults.

Introduction:: The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged  60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years.

Persistence of Yellow Fever vaccine-induced antibodies after cord blood stem cell transplant.

We report the case of a cord blood haematopoietic stem cell transplant recipient who was vaccinated for Yellow Fever (YF) 7 days before initiating chemotherapy and had persistent YF antibodies more than 3 years after vaccination. Since the stem cell donor was never exposed to wild YF or to the YF vaccine, and our patient was not exposed to YF or revaccinated, this finding strongly suggests the persistence of recipient immunity. We briefly discuss potential consequences of incomplete elimination of recipient's leukocytes following existing haematopoietic cancer treatments.

Yellow Fever 17DD Vaccine Virus Infection Causes Detectable Changes in Chicken Embryos.

The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model.

Booster dose after 10 years is recommended following 17DD-YF primary vaccination.

A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination.

A DNA vaccine against yellow fever virus: development and evaluation.

Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal.

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 Human Hookworm Vaccine.

Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy.

Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles.

Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production.

[Vaccines, immunization and technological innovation: an update].

The smallpox worldwide eradication was the major world public health achievement. The binomial - vaccines and immunization - continues to demonstrate very high performance in the prevention and control of other diseases preventable by vaccination. The new global initiatives on vaccination, such as GAVI, have made possible the introduction of new and important vaccines preventing million of children deaths in the poorest countries in the world.

Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication.

This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi).

Evidence for interferon production and its correlation with YF 17DD vaccine virus yields in primary chick embryo cells.

Early experiments have resulted in the establishment of an efficient methodology for the production of a yellow fever vaccine in chicken embryo fibroblasts (CEF) using the 17DD virus strain [Freire, M.S., Mann, G.

Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial.

Objective: To compare the reactogenicity of three yellow fever (YF) vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots) and placebo.

Methods: The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered ("day 0") following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types.

Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized trial.

Objective: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots).

Methods: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind).