When is it best to use dose-sparing monkeypox vaccination strategies to protect more people?

When is it best to use dose-sparing monkeypox vaccination strategies to protect more people?

In a recently published study medRxiv * Preprint Server, researchers evaluated dose-sparing strategies for monkeypox (MPX) vaccination using mathematical modeling.

Lernen: Bewertung der Anwendung dosissparender Impfstrategien für Affenpocken. Bildnachweis: LookerStudio/Shutterstock

background

The ongoing MPX outbreak was declared a public health emergency by the World Health Organization in July 2022. As of September 2022, more than 50,000 MPX cases have been recorded worldwide, with the United States (US) alone accounting for >21,000 cases. Most cases have been observed in men who have sex with men (MSM), bisexual and homosexual men.

The modified Vaccinia Ankara (MVA) [JYNNEOS] and ACAM2000 vaccines have been approved in the United States for MPX prevention. The Food and Drug Administration has approved a lower dose regimen in which each vaccine vial can be used for up to five (partial) doses. Still, recent studies have reported mixed efficacy results, raising concerns about whether fractional dosing of the MVA vaccine is the best use of its limited supply.

The study and results

In the current study, researchers used mathematical models to examine scenarios in which fractional dosing of the MVA vaccine would be optimal. The model of MPX transmission among the MSM population in Seattle, Washington was adopted from the model of human immunodeficiency virus (HIV) transmission. The population included 65,000 men, divided into age and risk groups. There were around 8,000 men in the high-risk group with an increased need for vaccination.

In the primary scenario, researchers simulated vaccination with 2,500 or 7,500 full-dose vaccine vials over five weeks and assumed that each vial could be used as 3.5 doses, enough for 8,750 or 26,250 people, respectively. Vaccine efficacy (VE) for a full-dose MVA vaccine was estimated to be 85% against MPX infection. Low and high partial dose VE scenarios were simulated, corresponding to 40% and 80% VE of the full dose MVA.

Additionally, scenarios with 5,000 or 10,000 full-dose MVA vials were simulated, with vaccination starting with a five or ten week delay. The partial dose VE ranged from 17% to 85%. In all scenarios, the high-risk population received vaccination first, and the remaining doses were used for low-risk populations.

When only 2500 vaccine vials were available, sufficient for 31% of (the 8000) high-risk individuals, dose sparing prevented more infections than full-dose immunization when partial dose VE was >34%. In this scenario, 13% fewer infections were predicted when dose-sparing was implemented.

In contrast, when 7500 vaccines were available, sufficient to vaccinate 94% of high-risk individuals, it was predicted that full-dose vaccination would outperform this dose-sparing strategy with a low partial-dose VE of 34%. In this scenario, dose-sparing would have caused three times as many infections as full-dose vaccination campaigns.

Assuming a high partial dose VE of 68% that maintains 80% of the full dose VE, dose sparing would always be better or comparable to full dose vaccination campaigns. In this case, with a limited supply (2500), partial doses would have caused 69% fewer infections overall and 77% fewer infections at the peak compared to full-dose campaigns.

In the same case, with more vaccines available (7500 vials), dose-sparing and full-dose strategies would have been comparable in effectiveness, but the dose-sparing strategy would cause 5.3% more infections at peak. In the optimistic scenario of equivalent VE of fractionated and full-dose vaccine with limited supply (2500 vials), it was predicted that fractional dosing would prevent 30% or more infections over six months than no vaccination.

However, when 7500 vials were available, partial dosing would have prevented 5% more infections than the full-dose strategy if both full- and partial-dose campaigns had been conducted without delays. At a very low partial-dose VE of 17%, dose-sparing would have caused more infections than full-dose campaigns in all scenarios.

Conclusions

In summary, the results suggest that in cases of limited supply of the MPX-MVA vaccine, a partial dose VE threshold exists above which dose sparing could prevent more infections than a full dose vaccination campaign. This partial dose VE threshold increased as vaccine supply increased.

The VE threshold for split doses was <34% with limited (2500) vaccines available, but increased to 68% when 7500 vaccines were available. The increase in infections prevented was minimal when the number of vaccines exceeded the number of people at high risk. Together, these results demonstrated that fractional dosing maintained moderate efficacy during times of limited MVA vaccine supply.

*Important NOTE

medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or treated as established information.

Reference:

• Dimitrov, D., Adamson, B. und Matrajt, L. (2022) „Bewertung der Verwendung dosissparender Impfstrategien für Affenpocken“. medRxiv. doi: 10.1101/2022.11.04.22281966. https://www.medrxiv.org/content/10.1101/2022.11.04.22281966v1

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