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.[citation needed]

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

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### In the context of limited healthcare budgets

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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

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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

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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.[citation needed]

## References

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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. ^ a b 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. ^ a b 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).