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Provinces should consider “dose sparing strategies” to stretch limited monkeypox vaccine supplies.

NACI greenlights second doses, dose splitting of monkeypox vaccine

Canada’s National Advisory Committee on Immunization (NACI) is strongly recommending “dose sparing strategies” to offer more people the monkeypox vaccine, including second doses.

Imvamune, the only monkeypox vaccine available in Canada, normally should be given subcutaneously in two doses, 28 days apart. But due to limited supplies, provinces have only offered first doses to people at higher risk of infection, including sex workers and men who have sex with men.

In updated guidance, NACI strongly recommends that second doses should be offered “when supply is not constrained.”

While supplies are limited, provinces should consider “dose sparing strategies,” including prioritizing first doses, even when that means some people may wait longer than 28 days for a second shot, as well as giving one-fifth the normal dose intradermally to stretch supplies further.

Although evidence supporting these strategies is limited, NACI says federal modelling suggests that extending the time between doses and giving less vaccine for the second dose “could have short-term public health benefits in preventing infections while vaccine supply is constrained as long as three or more fractional doses could be extracted from each vial.”

NACI factored in the need for more people to be vaccinated against monkeypox before exposure to the virus. Efforts to target vaccines to people after exposure have “proven challenging,” NACI says, because many people don’t realize they’ve had contact with an infected person.

So far, more than 50,000 people in Canada have received their first doses of Imvamune, and numbers of new cases are declining across the country and around the world.

Preliminary data from the United States shows people at risk of monkeypox who didn’t receive the vaccine were 14 times more likely to be infected than those who received a single dose.

However, breakthrough cases after a single dose are emerging, says NACI.

“Fractional” second doses are already available in the United States and Europe. To be most effective, these smaller, off-label doses should be administered intradermally, or into the skin, which is rife with specialized defensive cells, rather than subcutaneously, into the fatty tissue beneath.

Smaller intradermal injections can trigger similar immune responses to full doses administered subcutaneously, but they also pose a higher risk of severe local reactions, NACI cautioned.

Before offering intradermal injections, provinces should ensure that staff receive adequate training in administering the shots and have protocols to reduce the risk of cross-contamination and waste when splitting doses.

NACI’s recommendations on dose sparing don’t apply to people who are moderately or severely immunocompromised, who should be prioritized for both shots and receive full doses subcutaneously. People under 18 and those at risk of keloid scars should also receive the shots subcutaneously.

Ontario will offer second doses of the monkeypox vaccine following NACI’s recommendations. The province has the highest number of cases in Canada with 674 confirmed as of September 27, mostly occurring among men in the Toronto area.

NACI will continue reviewing evidence on the vaccine’s safety and effectiveness, including real-world evidence from other jurisdictions offering intradermal fractional doses.

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