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In a recent study posted to the medRxiv* preprint server, researchers evaluated dose-sparing strategies for monkeypox (MPX) vaccination using mathematical modeling.

Background

The ongoing MPX outbreak was declared a public health emergency in July 2022 by the World Health Organization. More than 50,000 MPX cases were recorded worldwide by September 2022, with the United States (US) alone accounting for > 21, triamcinolone cream 80gm 0.1 000 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 for MPX prevention in the US. The Food and Drug Administration has authorized a lower dose regimen, wherein each vaccine vial can be used for up to five (fractional) doses. Nevertheless, recent studies reported mixed efficacy results, raising concerns if fractional dosing of the MVA vaccine is the best use of its limited supply.

The study and findings

In the current study, researchers used mathematical modeling to explore scenarios wherein 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 comprised 65,000 men, categorized into age groups and risk groups. There were around 8,000 men in the high-risk group with a greater need to vaccinate.

In the primary scenario, the researchers simulated vaccination with 2500 or 7500 full-dose vaccine vials over five weeks and assumed that each vial could be used as 3.5 doses sufficient for 8750 or 26250 individuals, respectively. The vaccine effectiveness (VE) for a full-dose MVA vaccine was estimated to be 85% against MPX infection. Low and high fractional dose VE scenarios were simulated that corresponded to 40% and 80% VE of the full dose MVA.

In addition, scenarios with 5000 or 10000 full-dose MVA vials were simulated, with the vaccination commencing with a five- or 10-week delay. The fractional dose VE ranged between 17% and 85%. The high-risk population received vaccination first in all scenarios, 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 if the fractional dose VE was > 34%. In this scenario, 13% fewer infections were projected when dose-sparing was implemented.

Contrastingly, when 7500 vaccines were available, sufficient to vaccinate 94% of high-risk individuals, full-dose vaccination was projected to outperform this dose-sparing strategy with a low fractional dose VE of 34%. In this scenario, dose-sparing would have caused thrice as many infections as full-dose vaccination campaigns.

For the assumption of a high fractional dose VE of 68%, retaining 80% of full-dose VE, dose-sparing would always outperform or be comparable to full-dose vaccination campaigns. In this case, with a limited supply (2500), fractional doses would have caused 69% fewer infections overall and 77% fewer at the peak relative to full-dose campaigns.

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

Nevertheless, when 7500 vials were available, fractional dosing would have averted 5% more infections than the full-dose strategy when both full- and fractional-dose campaigns were implemented with no delays. For a very low fractional dose VE of 17%, dose-sparing would have caused more infections than full-dose campaigns in all scenarios.

Conclusions

In summary, the findings suggested that in the cases of a limited supply of the MPX MVA vaccine, a VE threshold exists for fractional doses, above which dose-sparing could avert more infections than a full-dose vaccination campaign. This fractional dose VE threshold increased with the increase in vaccine supply.

The VE threshold for fractional doses was < 34% with limited (2500) vaccines available but increased to 68% when 7500 vaccines were available. The gains in infections prevented were minimum when the number of vaccines exceeded the number of high-risk individuals. Together, these results indicated that fractional dosing retained moderate effectiveness in times of limited MVA vaccine supply.

*Important notice

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

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.