Faculty Opinions recommendation of Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report.

Author(s):  
Pedro Legua Leiva
2019 ◽  
Vol 381 (5) ◽  
pp. 444-454 ◽  
Author(s):  
Rebecca M. Casey ◽  
Jennifer B. Harris ◽  
Steve Ahuka-Mundeke ◽  
Meredith G. Dixon ◽  
Gabriel M. Kizito ◽  
...  

2016 ◽  
Author(s):  
Joseph T. Wu ◽  
Corey M. Peak ◽  
Gabriel M. Leung ◽  
Marc Lipsitch

BackgroundThe ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July-August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission.MethodsWe estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July-August 2016 with different age cutoff for fractional-dose vaccines.FindingsWe estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%.InterpretationDose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.FundingNIH-MIDAS, HMRF-Hong Kong


2018 ◽  
Vol 379 (7) ◽  
pp. 603-605 ◽  
Author(s):  
Kirsten Vannice ◽  
Annelies Wilder-Smith ◽  
Joachim Hombach

2019 ◽  
Vol 171 (2) ◽  
pp. 145 ◽  
Author(s):  
Annelies Wilder-Smith ◽  
Alan Barrett ◽  
Kirsten Vannice ◽  
Joachim Hombach

2021 ◽  
Vol 15 (11) ◽  
pp. e0010002
Author(s):  
Adriana Coracini Tonacio ◽  
Tatiana do Nascimento Pedrosa ◽  
Eduardo Ferreira Borba ◽  
Nadia Emi Aikawa ◽  
Sandra Gofinet Pasoto ◽  
...  

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).


2019 ◽  
Vol 26 (6) ◽  
Author(s):  
Anna H E Roukens ◽  
Leo G Visser

Abstract Rationale for review: The global yellow fever vaccine supply is insufficient to provide full-dose vaccination to millions threatened by outbreaks. Given the excess of live-attenuated 17D yellow fever virus in the current single dose vials, dose sparing would increase available vaccine doses manifold. Fractional-dose yellow fever vaccination is now accepted as an emergency solution, as short-term protection has been confirmed in an outbreak situation in the Democratic Republic of Congo, but broader application of this dose-sparing strategy is still not recommended. In this review, important knowledge gaps that hamper this application such as long-term protection after fractional-dose vaccination, safety, comparability across different genetic backgrounds and different World Health Organization-licensed yellow fever vaccines and immunogenicity in infants are addressed. Main findings: Recently, published results on long-term protection after fractional-dose vaccination in healthy young volunteers indicate that if a person mounts a protective response shortly after vaccination, the protective response will persist for 10 years and possibly longer. It also appears that fractional-dose vaccination does not elicit more serious adverse events than standard dose vaccination. Short-term immunogenicity studies are currently underway in specific populations (infants, human immunodeficiency virus (HIV)-infected persons and healthy adults living in Uganda and Kenya), of which the results will become available in 2021–22. Conclusions: Available results on long-lasting immunogenicity of fractional-dose yellow fever vaccination are encouraging, although confirmation is required in larger populations including young children living in yellow fever endemic areas.


Sign in / Sign up

Export Citation Format

Share Document