scholarly journals Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

2016 ◽  
Author(s):  
Joseph T. Wu ◽  
Corey M. Peak ◽  
Gabriel M. Leung ◽  
Marc Lipsitch
Keyword(s):  
Yellow Fever ◽  
Vaccine Efficacy ◽  
Attack Rate ◽  
Standard Dose ◽  
Vaccination Campaign ◽  
Yellow Fever Vaccine ◽  
Dose Fractionation ◽  
Reproductive Number ◽  
Fractional Dose ◽  
Dose Vaccine

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

scholarly journals Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial

2016 ◽  
Vol 23 (3) ◽  
pp. 228-235 ◽  
Author(s):  
Andrew J. Dunning ◽  
Carlos A. DiazGranados ◽  
Timothy Voloshen ◽  
Branda Hu ◽  
Victoria A. Landolfi ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Efficacy ◽  
Standard Dose ◽  
The Elderly ◽  
High Dose ◽  
Efficacy Trial ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Immunologic Assays ◽  
Dose Vaccine

ABSTRACTAlthough a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. A recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired A/H3N2 influenza illness. The high-dose vaccine induced significantly higher antibody titers than the standard-dose vaccine for all assays. For the hemagglutination inhibition assay, a titer of 40 was found to correspond with 50% protection when the assay virus was antigenically well matched to the circulating virus—the same titer as is generally recognized for 50% protection in younger adults. A dramatically higher titer was required for 50% protection when the assay virus was a poor match to the circulating virus. With the well-matched virus, some protection was seen at the lowest titers; with the poorly matched virus, high levels of protection were not achieved even at the highest titers. Strong associations were also seen between virus neutralization test titers and protection, but reliable estimates for 50% protection were not obtained. An association was seen between titers of an enzyme-linked lectin assay for antineuraminidase N2 antibodies and protection; in particular, the proportion of treatment effect explained by assay titer in models that included both this assay and one of the other assays was consistently higher than in models that included either assay alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01427309.)

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

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).

scholarly journals Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak — Final Report

2019 ◽  
Vol 381 (5) ◽  
pp. 444-454 ◽  
Author(s):  
Rebecca M. Casey ◽  
Jennifer B. Harris ◽  
Steve Ahuka-Mundeke ◽  
Meredith G. Dixon ◽  
Gabriel M. Kizito ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Final Report ◽  
Fractional Dose ◽  
Dose Vaccine

Safety of the yellow fever vaccine during the September 2001 mass vaccination campaign in Abidjan, Ivory Coast

Vaccine ◽  
2004 ◽  
Vol 23 (2) ◽  
pp. 156-162 ◽  
Author(s):  
J FITZNER ◽  
D COULIBALY ◽  
D EKRAKOUADIO ◽  
J CLAUDEYAVO ◽  
Y LOUKOU ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Ivory Coast ◽  
Vaccination Campaign ◽  
Mass Vaccination ◽  
Yellow Fever Vaccine ◽  
Mass Vaccination Campaign

Fractional-dose yellow fever vaccination: an expert review

2019 ◽  
Vol 26 (6) ◽  
Author(s):  
Anna H E Roukens ◽  
Leo G Visser
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
World Health ◽  
Yellow Fever Vaccine ◽  
Short Term ◽  
Protective Response ◽  
Fractional Dose ◽  
Dose Sparing ◽  
Yellow Fever Vaccination

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.

scholarly journals Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomized, double-blind, non-inferiority trial

2020 ◽  
Author(s):  
Aitana Juan-Giner ◽  
Derick Kimathi ◽  
Kyra H. Grantz ◽  
Mainga M. Hamaluba ◽  
Patrick Kazooba ◽  
...  
Keyword(s):  
International Development ◽  
Yellow Fever ◽  
Standard Dose ◽  
Adult Population ◽  
Neutralizing Antibody ◽  
Yellow Fever Vaccine ◽  
Absolute Difference ◽  
Outbreak Response ◽  
Double Blind ◽  
Link Type

AbstractBackgroundYellow fever vaccine stocks have been insufficient to cover exceptional demands for outbreak response. Fractional dosing evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared to standard dose of each of the four WHO-prequalified yellow fever vaccines produced from three substrains.MethodsWe conducted a randomized, double-blind, non-inferiority trial in Mbarara, Uganda and Kilifi, Kenya. 960 participants aged 18-59 years without history of yellow fever vaccination or infection were recruited from communities and randomized to a vaccine and dosage. Vaccine was administered subcutaneously by unblinded nurse. Other study personnel and participants were blinded to vaccine allocation. Primary immunogenicity outcome, seroconversion, was measured in the per-protocol population; safety outcomes included all vaccinated participants. We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared to standard dose arms 28 days post-vaccination. Seroconversion was ≥4-fold rise in neutralizing antibody titers measured by 50% plaque reduction neutralization test.ClinicalTrials.gov Identifier: NCT02991495, completed.FindingsBetween 6th November 2017 and 21st February 2018, 960 participants, total sample goal, were randomized. The primary per-protocol analysis includes 899 participants, 110 to 117 participants per arm. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1.71% (95%CI: −2.60, 5.28) for Bio-Manguinhos, −0.90% (95%CI: −4.24, 3.13) for Chumakov Institute, 1.82% (95%CI: −2.75, 5.39) for Institut Pasteur de Dakar, 0.0% (95%CI: −3.32, 3.29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common related AEs were headache (22.2%), fatigue (13.7%), myalgia (13.3%) and self-reported fever (9.0%). There were no safety concerns.InterpretationThese results support fractional dosing of all WHO-prequalified yellow fever vaccines for the general adult population for outbreak response in situations of vaccine shortage.FundingThe study was funded by Médecins Sans Frontières Foundation, Wellcome Trust (grant no. 092654) and the UK Department for International Development. Vaccines were donated in kind.

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