Fractional dose vaccination

Fractional dose vaccination[1][2] is a strategy to reduce the dose of a vaccine to achieve a vaccination policy goal that is more difficult to achieve with conventional vaccination approaches, including deploying a vaccine faster in a pandemic,[3] reaching more individuals in the setting of limited healthcare budgets, or minimizing side effects due to the vaccine.

Fractional dose vaccination exploits the nonlinear dose-response characteristics of a vaccine: If two persons can be vaccinated instead of one, but each one gets 2/3 of the protective efficacy, there is a net benefit at society scale for reducing the number of infections. If the healthcare budget is limited or only a limited amount of vaccine is available during the early phase of a pandemic, this can make a difference for the total number of infections.

Fractional dose vaccination uses a fraction of the standard dose of a regular vaccine that is administered by the same, or an alternative route (often subcutaneously or intradermally).[4]

Fractional dose vaccination has been used or proposed in a number of relevant infectious poverty diseases including yellow fever,[2] poliomyelitis,[5] COVID-19.[6]

Use

In the context of limited healthcare budgets

During the 2016 yellow fever outbreak in Angola and the Democratic Republic of the Congo, the WHO approved the use of fractional dose vaccination to deal with a potential shortage of vaccine.[7] In August 2016, a large vaccination campaign in Kinshasa used 1/5 of the standard vaccine dose.[8] In 2018 it was reported that fractional dose vaccination with 1/5 of the standard vaccine dose, administered intradermally, conferred protection for 10 years, as documented by a randomized clinical trial.[9]

In Poliomyelitis, fractional dose vaccination has been shown to be effective while reducing overall cost,[10] rendering polio vaccination available to more individuals.

In the Covid-19 pandemic

In a pandemic wave, fractional dose vaccination is considered to accelerate widespread access to vaccination when vaccine supply is limited:

In the COVID-19 pandemic, epidemiologic models predict a major benefit of personalized fractional dose vaccination strategies with certain vaccines in terms of case load, deaths, and shortening of the pandemic.[3][11]

To reduce side effects

In some segments of the population, disease risk is lower but specific vaccine side effect risks may be increased.[12] In such subpopulations, fractional dose vaccination might optimize the benefit-risk ratio of vaccination for an individuum and optimize the cost-benefit relation for society.

References
  1. Chen, Zhimin; Liu, Kaihui; Liu, Xiuxiang; Lou, Yijun (2020-02-07). "Modelling epidemics with fractional-dose vaccination in response to limited vaccine supply". Journal of Theoretical Biology. 486: 110085. doi:10.1016/j.jtbi.2019.110085. hdl:10397/94076. ISSN 0022-5193. PMID 31758966. S2CID 208254350.
  2. Vannice, Kirsten; Wilder-Smith, Annelies; Hombach, Joachim (2018-08-16). "Fractional-Dose Yellow Fever Vaccination — Advancing the Evidence Base". New England Journal of Medicine. 379 (7): 603–605. doi:10.1056/NEJMp1803433. ISSN 0028-4793. PMID 29995585. S2CID 205114579.
  3. Hunziker, Patrick (2021-07-24). "Personalized-dose Covid-19 vaccination in a wave of virus Variants of Concern: Trading individual efficacy for societal benefit". Precision Nanomedicine. 4 (3). doi:10.33218/001c.26101. ISSN 2639-9431.
  4. Schnyder, Jenny L.; De Pijper, Cornelis A.; Garcia Garrido, Hannah M.; Daams, Joost G.; Goorhuis, Abraham; Stijnis, Cornelis; Schaumburg, Frieder; Grobusch, Martin P. (2020-09-01). "Fractional dose of intradermal compared to intramuscular and subcutaneous vaccination - A systematic review and meta-analysis". Travel Medicine and Infectious Disease. 37: 101868. doi:10.1016/j.tmaid.2020.101868. ISSN 1477-8939. PMC 7474844. PMID 32898704.
  5. Resik, Sonia; Tejeda, Alina; Sutter, Roland W.; Diaz, Manuel; Sarmiento, Luis; Alemañi, Nilda; Garcia, Gloria; Fonseca, Magilé; Hung, Lai Heng; Kahn, Anna-Lea; Burton, Anthony (2013-01-31). "Priming after a Fractional Dose of Inactivated Poliovirus Vaccine". New England Journal of Medicine. 368 (5): 416–424. doi:10.1056/NEJMoa1202541. ISSN 0028-4793. PMID 23363495.
  6. Hunziker, Patrick (2021-03-07). "Vaccination strategies for minimizing loss of life in Covid-19 in a Europe lacking vaccines". medRxiv 10.1101/2021.01.29.21250747v6.
  7. World Health Organization (2016-07-20). "Fractional dose yellow fever vaccine as a dose-sparing option for outbreak response". WHO Secretariat Information Paper. hdl:10665/246236.
  8. "Millions protected in Africa's largest-ever emergency yellow fever vaccination campaign". WHO News Release. 2 September 2016. Retrieved 2022-06-08.
  9. Roukens, Anna H.E.; van Halem, Karlijn; de Visser, Adriëtte W.; Visser, Leo G. (2018-11-27). "Long-Term Protection After Fractional-Dose Yellow Fever Vaccination". Annals of Internal Medicine. 169 (11): 761–765. doi:10.7326/m18-1529. ISSN 0003-4819. PMID 30476963. S2CID 53737386.
  10. Nelson, Katherine S.; Janssen, Julia M.; Troy, Stephanie B.; Maldonado, Yvonne (2012-01-05). "Intradermal fractional dose inactivated polio vaccine: A review of the literature". Vaccine. 30 (2): 121–125. doi:10.1016/j.vaccine.2011.11.018. ISSN 0264-410X. PMID 22100886.
  11. Hunziker, Patrick (2021-07-24). "Personalized-dose Covid-19 vaccination in a wave of virus Variants of Concern: Trading individual efficacy for societal benefit". Precision Nanomedicine. 4 (3): 805–820. doi:10.33218/001c.26101.
  12. Wallace, Megan; Oliver, Sara (2021-06-23). "COVID-19 mRNA vaccines in adolescents and young adults: Benefit-risk discussion" (PDF).
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