Safety and immunogenicity of a primary yellow fever vaccination under low-dose methotrexate therapy—a prospective multi-centre pilot study1

Abstract Background More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during immunosuppression are scarce. The aim of this study was to compare the safety and immunogenicity of a primary YFVV between travellers on methotrexate and controls. Methods We conducted a prospective multi-centre controlled observational study from 2015 to 2017 in six Swiss travel clinics. 15 adults (nine with rheumatic diseases, five with dermatologic conditions and one with a gastroenterological disease) on low-dose methotrexate (≤20 mg/week) requiring a primary YFVV and 15 age and sex-matched controls received a YFVV. Solicited/unsolicited adverse reactions were recorded, YFV-RNA was measured in serum samples on Days 3, 7, 10, 14, 28 and neutralizing antibodies on Days 0, 7, 10, 14, 28. Results Patients´ and controls’ median ages were 53 and 52 years; 9 patients and 10 controls were female. 43% of patients and 33% of controls showed local side effects (P = 0.71); 86% of patients and 66% of controls reported systemic reactions (P = 0.39). YFV-RNA was detected in patients and controls on Day 3–10 post-vaccination and was never of clinical significance. Slightly more patients developed YFV-RNAaemia (Day 3: n = 5 vs n = 2, Day 7: n = 9 vs n = 7, Day 10: n = 3 vs n = 2, all P > 0.39). No serious reactions occurred. On Day 10, a minority of vaccinees was seroprotected (patients: n = 2, controls: n = 6). On Day 28, all vaccinees were seroprotected. Conclusions First-time YFVV was safe and immunogenic in travellers on low-dose methotrexate. Larger studies are needed to confirm these promising results.

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Serological response to rabies virus induced by commercial vaccines in cattle

Ciência Rural ◽

10.1590/0103-8478cr20161044 ◽

2017 ◽

Vol 47 (10) ◽

Author(s):

Mathias Martins ◽

João Motta de Quadros ◽

Eduardo Furtado Flores ◽

Rudi Weiblen

Keyword(s):

Rabies Virus ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Booster Vaccination ◽

Serological Response ◽

Serum Samples ◽

Anamnestic Response ◽

Post Vaccination ◽

Antibody Titers ◽

One Year

ABSTRACT: The antibody response to rabies virus (RABV) induced by commercial vaccines in heifers was investigated. For this, 84 heifers were vaccinated twice (30 days interval) with each of four vaccines (G1 = 14 animals; G2 = 24; G3 = 22 and G4 = 24) and received a booster vaccination 360 days later. Serum samples collected at different intervals after vaccination and 30 days after booster were submitted to a virus neutralizing (VN) assay for RABV antibodies. Thirty days after the second vaccine dose, 92% of the immunized animals presented VN titers ≥0.5UI/mL (geometric medium titers [GMT] 1.7 to 3.8UI/mL). At the day of the booster (360 days post-vaccination); however, the percentage of animals harboring antibody titers ≥0.5UI/mL had dropped to 31% (0-80% of the animals, depending on the vaccine), resulting in lower GMT (0.1 to 0.6UI/mL). Booster vaccination at day 360 resulted in a detectable anamnestic response in all groups, resulting in 83% of animals (65 to 100%) harboring VN titers ≥0.5UI/mL thirty days later (GMT 0.6 to 4.3UI/mL). These results indicated that these vaccines were able to induce an adequate anti-RABV response in all animals after prime vaccination (and after booster as well). However, the titers decreased, reaching titers <0.5UI/mL in approximately 70% of animals within the interval before the recommended booster. Thus, booster vaccination for rabies in cattle using the current vaccines should be performed before the recommended one-year interval, as to maintain neutralizing antibodies levels in most vaccinated animals.

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

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s1678-9946201759002 ◽

2017 ◽

Vol 59 (0) ◽

Cited By ~ 8

Author(s):

Karina Takesaki Miyaji ◽

Vivian Iida Avelino-Silva ◽

Marisol Simões ◽

Marcos da Silva Freire ◽

Carlos Roberto de Medeiros ◽

...

Keyword(s):

Yellow Fever ◽

Neutralizing Antibodies ◽

Yellow Fever Virus ◽

Fever Virus

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Ontogeny of different subsets of yellow fever virus-specific circulatory CXCR5+ CD4+ T cells after yellow fever vaccination

Scientific Reports ◽

10.1038/s41598-020-72610-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Quinn DeGottardi ◽

Theresa J. Gates ◽

Junbao Yang ◽

Eddie A. James ◽

Uma Malhotra ◽

...

Keyword(s):

T Cells ◽

Yellow Fever ◽

Germinal Center ◽

Yellow Fever Virus ◽

Fever Virus ◽

Mass Cytometry ◽

Follicular Helper ◽

Potential Biomarker ◽

Yellow Fever Vaccination ◽

The Relationship

Abstract Monitoring the frequency of circulatory CXCR5+ (cCXCR5+) CD4+ T cells in periphery blood provides a potential biomarker to draw inferences about T follicular helper (TFH) activity within germinal center. However, cCXCR5+ T cells are highly heterogeneous in their expression of ICOS, PD1 and CD38 and the relationship between different cCXCR5 subsets as delineated by these markers remains unclear. We applied class II tetramer reagents and mass cytometry to investigate the ontogeny of different subsets of cCXCR5+ T cell following yellow fever immunization. Through unsupervised analyses of mass cytometry data, we show yellow fever virus-specific cCXCR5 T cells elicited by vaccination were initially CD38+ICOS+PD1+, but then transitioned to become CD38+ICOS−PD1+ and CD38−ICOS−PD1+ before coming to rest as a CD38−ICOS−PD1− subset. These results imply that most antigen-specific cCXCR5+ T cells, including the CD38−ICOS−PD1− CXCR5+ T cells are derived from the CXCR5+CD38+ICOS+PD1+ subset, the subset that most resembles preTFH/TFH in the germinal center.

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A Yellow Fever Virus 17D Infection and Disease Mouse Model Used to Evaluate a Chimeric Binjari-Yellow Fever Virus Vaccine

Vaccines ◽

10.3390/vaccines8030368 ◽

2020 ◽

Vol 8 (3) ◽

pp. 368 ◽

Cited By ~ 3

Author(s):

Kexin Yan ◽

Laura J. Vet ◽

Bing Tang ◽

Jody Hobson-Peters ◽

Daniel J. Rawle ◽

...

Keyword(s):

Weight Loss ◽

Mouse Model ◽

Yellow Fever ◽

Virus Vaccine ◽

Neutralizing Antibodies ◽

Yellow Fever Virus ◽

Fever Virus ◽

Liver Pathology ◽

Vaccine Production ◽

Mosquito Cells

Despite the availability of an effective, live attenuated yellow fever virus (YFV) vaccine (YFV 17D), this flavivirus still causes up to ≈60,000 deaths annually. A number of new approaches are seeking to address vaccine supply issues and improve safety for the immunocompromised vaccine recipients. Herein we describe an adult female IFNAR-/- mouse model of YFV 17D infection and disease that recapitulates many features of infection and disease in humans. We used this model to evaluate a new YFV vaccine that is based on a recently described chimeric Binjari virus (BinJV) vaccine technology. BinJV is an insect-specific flavivirus and the chimeric YFV vaccine (BinJ/YFV-prME) was generated by replacing the prME genes of BinJV with the prME genes of YFV 17D. Such BinJV chimeras retain their ability to replicate to high titers in C6/36 mosquito cells (allowing vaccine production), but are unable to replicate in vertebrate cells. Vaccination with adjuvanted BinJ/YFV-prME induced neutralizing antibodies and protected mice against infection, weight loss and liver pathology after YFV 17D challenge.

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Detection of Anti-Yellow Fever Virus Immunoglobulin M Antibodies at 3–4 Years Following Yellow Fever Vaccination

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.2012.12-0182 ◽

2012 ◽

Vol 87 (6) ◽

pp. 1112-1115 ◽

Cited By ~ 15

Author(s):

Katherine B. Gibney ◽

Olga I. Kosoy ◽

Marc Fischer ◽

Srilatha Edupuganti ◽

Robert S. Lanciotti ◽

...

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Immunoglobulin M ◽

Fever Virus ◽

Yellow Fever Vaccination

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Yellow fever virus isolated from a fatal post vaccination event: an experimental comparative study with the 17DD vaccine strain in the Syrian hamster (Mesocricetus auratus)

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822004000700011 ◽

2004 ◽

Vol 37 (suppl 2) ◽

pp. 69-74 ◽

Cited By ~ 6

Author(s):

Sueli Guerreiro Rodrigues ◽

Amélia Paes de Andrade Travassos da Rosa ◽

Ricardo Galler ◽

Vera Lúcia Reis de Souza Barros ◽

Conceição de Maria Almeida Vieira ◽

...

Keyword(s):

Yellow Fever ◽

Vaccine Strain ◽

Yellow Fever Virus ◽

Mesocricetus Auratus ◽

Virus Antigen ◽

Fever Virus ◽

Wild Type ◽

Post Vaccination ◽

The Brain ◽

Virus Strains

In order to investigate the pathogenicity of the virus strain GOI 4191 that was isolated from a fatal adverse event after yellow fever virus (YFV) vaccination, an experimental assay using hamsters (Mesocricetus auratus) as animal model and YFV 17DD vaccine strain as virus reference was accomplished. The two virus strains were inoculated by intracerebral, intrahepatic and subcutaneous routes. The levels of viremia, antibody response, and aminotransferases were determined in sera; while virus, antigen and histopathological changes were determined in the viscera. No viremia was detected for either strain following infection; the immune response was demonstrated to be more effective to strain GOI 4191; and no significant aminotransferase levels alterations were detected. Strain GOI 4191 was recovered only from the brain of animals inoculated by the IC route. Viral antigens were detected in liver and brain by immunohistochemical assay. Histothological changes in the viscera were characterized by inflammatory infiltrate, hepatocellular necrosis, and viral encephalitis. Histological alterations and detection of viral antigen were observed in the liver of animals inoculated by the intrahepatic route. These findings were similar for both strains used in the experiment; however, significant differences were observed from those results previously reported for wild type YFV strains.

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Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma samples for accurate measurement of anti-Yellow fever virus neutralizing antibodies

Journal of Immunological Methods ◽

10.1016/j.jim.2017.05.002 ◽

2017 ◽

Vol 448 ◽

pp. 9-20 ◽

Cited By ~ 2

Author(s):

Ana Carolina Campi-Azevedo ◽

Vanessa Peruhype-Magalhães ◽

Jordana Grazziela Coelho-dos-Reis ◽

Christiane Costa-Pereira ◽

Anna Yoshida Yamamura ◽

...

Keyword(s):

Yellow Fever ◽

Neutralizing Antibodies ◽

Yellow Fever Virus ◽

Fever Virus ◽

Plasma Samples ◽

Pre Treatment

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Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0010002 ◽

2021 ◽

Vol 15 (11) ◽

pp. e0010002

Author(s):

Adriana Coracini Tonacio ◽

Tatiana do Nascimento Pedrosa ◽

Eduardo Ferreira Borba ◽

Nadia Emi Aikawa ◽

Sandra Gofinet Pasoto ◽

...

Keyword(s):

Disease Activity ◽

Yellow Fever ◽

Neutralizing Antibodies ◽

Clinical Laboratory ◽

Seroconversion Rate ◽

Geometric Mean ◽

High Rate ◽

Yellow Fever Vaccine ◽

Post Vaccination ◽

Fractional Dose

Background Brazil faced a yellow fever(YF) outbreak in 2016–2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. Objective This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. Objective Methodology and principal findings: A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3–1292.2) vs.731 (95%CI 593.6–900.2), p<0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05). Objective Conclusion: Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas. Trial registration This clinical trial was registered with Clinicaltrials.gov (#NCT03430388).

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A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

10.1101/717181 ◽

2019 ◽

Author(s):

Niraj Mishra ◽

Robbert Boudewijns ◽

Michael A. Schmid ◽

Rafael Elias Marques ◽

Sapna Sharma ◽

...

Keyword(s):

Yellow Fever ◽

Japanese Encephalitis ◽

Neutralizing Antibodies ◽

Yellow Fever Virus ◽

Neutralizing Antibody ◽

Fever Virus ◽

Off Label Use ◽

Off Label ◽

Japanese Encephalitis Vaccine ◽

Label Use

ABSTRACTRecent massive outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being not prepared against future YFV epidemics. Here we report that a live-attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev® that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific non-neutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV non-structural (NS) proteins. Our findings reveal the importance of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev® can confer protection against two flaviviruses. This dual protection has implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev® may already be protected against YFV should outbreaks ever occur on that continent as feared by WHO.IMPORTANCEEfficient and safe vaccines exist against yellow fever (e.g. YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses. However, vaccine supply cannot cope with an increasing demand posed by massive urban outbreaks in recent years. Here we report that JE-CVax/Imojev®, a YFV-17D-based chimeric Japanese encephalitis vaccine also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev® may be considered. Moreover, wider use of JE-CVax/Imojev® in Asia may lower the risk of the much-feared YFV spill over to the continent. More in general chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses can be considered dual vaccines, for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection [inherent to current dengue vaccines and dengue vaccine candidates] could be designed.

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