The United States is considering shifting to intradermal injections of Monkeypox vaccine that could potentially stretch one dose of the approved MVA-BN vaccine, available only in limited quantities, into five doses, said US Food and Drug Administration Commissioner Robert Califf on Thursday.

He was speaking at a press briefing minutes after Xavier Becerra, US Secretary of Health and Human Services (HHS)  said he would declare a national health emergency over the monkeypox outbreak, which has now 6,600 confirmed cases in the United States – making it the global hotspot for the virus, followed by Spain and Germany. Some 26,000 cases had been reported worldwide, as of Thursday – not including several thousand suspected cases in central and western Africa, where the disease is endemic, but testing capacity remains poor.

“I will be declaring a public health emergency on Monkeypox.  We are prepared to take our response to the next level in addressing this virus,” said Becerra, speaking at a Thursday virtual press briefing in Washington, DC.

The United States currently holds about 1.4 million of the only  FDA-approved approved monkeypox vaccine in a strategic stockpile, which until recently had been intended for use mainly against any future smallpox threat, according to estimates by the global forecasting firm, Airfinity. HHS officials have already released about 1.1 million doses from the stockpile to cope with the emerging outbreak – which WHO declared a global health emergency on 23 July.

While the US has contracts to receive another 13 million doses in 2022, a significant proportion remain in bulk formulation, requiring fill-and-finish. Meanwhile, the only plant manufacturing the raw vaccine formula, produced by Denmark’s Bavarian Nordic, is closed for renovations until late 2022 – meaning that the global supply also is finite – in the face of a rapidly-developing outbreak.

‘Dose-sparing’ at critical inflection point

“Given the continued spread of the virus we are at a critical inflection point, dictating the need for continued solutions,” said Califf. While he said that the US was “working closely with the manufacturer to accelerate the delivery of doses,” another solution could be to “allow health care providers to use an existing 1 dose vial to administer up to 5 separate doses.

“Under the proposed approach, a fifth of the proposed dose would be introduced intradermally,” he said, explaining this is a more “shallow injection” than the typical subcutaneous injection.  But evidence suggests than if administered correctly, it could provide a powerful immune response for Monkeypox.

“This approach which we’re referring to, as dose sparing, would change the method of administration of Jynneos [the brand name for the MVA-BN vaccine], which is currently administered subcutaneously,” he said.

“Under the proposed approach, one-fifth of the current vaccines dose would be administered intradermally. There are some advantages to intradermal administration including an improved immune response to the vaccine,” he declared.  Although in fact the procedure is relatively rare, it is widely for hepatitis B vaccines in adults as well as the BCG tuberculosis vaccine in infants as well as children.

Califf said that a while a decision had not yet been made whether to move ahead with the dose-sparing strategy, “we are exploring all scientifically feasible options and we believe this could be a promising approach. … We look forward to sharing more information on the dose sparing approach in the days ahead.” 

Dose-sparing previously was recommended by WHO in the case of COVID vaccines, during much of 2021, when there was a global scarcity.

More than 600,000 vaccines already distributed in the United States

Becerra meanwhile said that of the 1.1 million BVA-MN vaccine doses committed by the US from its stockpiles to the health emergency, more than 600,000 doses have already been distributed to health providers around the country.

The US expects to receive another I50,000 finished vaccine doses in September, said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, adding that “we expedited those doses that they were previously scheduled to arrive in October. We anticipate continued delivery of additional doses in October, November and December,” she said, referring to vaccines now held in bulk by Bavarian Nordic, which need to undergo fill-and-finish.

As for testing, Becerra said that  “we have the capacity to administer some 80,000 tests a week, and that has continued to rise. … On treatments, we have deployed some 14,000 treatments of TPOXX, [Tecovirimat anti-viral treatment], and we have roughly 1,700,000 doses in our strategic stockpiles.” 

Meanwhile, the Director of the US Centers for Disease Control, Rochelle Walensky, said that the CDC estimates that there are about 1.6 -1.7 million Americans “who are at highest risk right now and that is the population that we have been focused on in terms of vaccination.” That includes groups such as men who have sex with men, as well as people already infected with HIV, and therefore with a potentially weakened immunity overall. 

Image Credits: Global Health , https://mvec.mcri.edu.au/references/intradermal-vaccination/.