Study raises questions about low-dose monkeypox vaccine approach

Late last week, a notable group of Dutch researchers published a preprint study of the neutralizing antibodies produced by two subcutaneous doses of Bavarian Nordic’s monkeypox vaccine, Jynneos (MVA), and reported that the dose-sparing strategy might not produce a very strong immune response.

“The series of primary MVA immunizations in non-sensitized individuals yielded relatively low levels of neutralizing antibodies, raising the question of whether vaccinated individuals are now protected and what are the correlates of protection against MPXV . [monkeypox virus] infection are,” they wrote. “At this time, it is unclear what the relatively low MPXV neutralizing titers mean for disease protection and transmissibility.

Subcutaneous or intradermal dosing is used in the United States as a means of using one-fifth of the usual vaccine dose, thus allowing many more people to be vaccinated using the same vaccine supply. Officials hoped the strategy would provide the same level of protection as a full dose of Jynneos.

But the new study shows low levels of antibody response after one and two doses of the subcutaneous vaccine.

Poor immune response after 1 dose

The small study, which included just 18 participants vaccinated subcutaneously – or just under the top layers of the skin – with two doses of Jynneos, alerted scientists around the world that use of the monkeypox vaccine, which n has never been extensively tested in humans, may not be as beneficial as previously hoped. The study has not yet been peer reviewed.

Corine GeurtsvanKessel, PhD, one of the study authors, told CIDRAP News that the work was important, not least because it showed almost no neutralizing antibodies 4 and 8 weeks after vaccination in those who had received the first of the recommended doses of 0.5 milliliters.

GeurtsvanKessel said that discovery alone raises doubts about fractional intradermal dosing, as well as delaying subcutaneous dosing to allow more people a first dose of the vaccine, two techniques used in the United States, which count. the most cases in the world.

“I don’t think advising a single vaccine [dose] is the way forward,” she said. “So one of the questions right now is whether vaccination will be the optimal tool to curb the epidemic. It is not expected to provide sterilizing immunity.”

US vaccine rollout is a ‘big gamble’

Stanford University fellow Abraar Karan, MD, MPH, said US officials made a big, if perhaps necessary, gamble when they launched the Jynneos campaign this summer. The vaccine has not been widely tested in humans and was developed for smallpox. And big questions remain about the protection and duration of injections for recipients.

“We have no idea about [the vaccine’s] impact on viral shedding or duration of protection,” Karan told CIDRAP. “And these big questions are clear if you read the CDC [US Centers for Disease Control and Prevention] website, but probably not clear to the general public. »

Karan said the United States faced a stark choice as cases began to surge earlier this summer: to use the relatively understudied Jynneos; using AKAM2000, a smallpox vaccine associated with more serious risks and side effects; or refrain from using any vaccine until more data have been obtained.

“It’s a real-world decision,” he said, “But the communication should have been, ‘A clear benefit for Jynneos probably outweighs the risk, but we don’t yet know how much the vaccine is beneficial” [in its current use].”

Karan said cohort studies, comparing people who received the vaccine, people with monkeypox cases and other groups, will be key to understanding how the vaccine works in real life. Already several European countries and the United States have announced such studies, but the results will not be available for months.

Until then, Karan said the United States needs to bolster its response to monkeypox by offering the vaccine and investing in antiviral treatments and faster point-of-care diagnostics.

Understanding Neutralizing Antibodies

Neutralizing antibodies are not the only tool the immune system can use to fight off a virus. The preprint did not study T cells.

But Yale researcher Akiko Iwasaki, PhD, said the neutralizing antibody study shows what the world doesn’t yet know. “We don’t know what titles are needed to protect against monkeypox,” she said. “More testing is needed to understand the correlates of protection against disease and see if vaccine strategies need to be changed to achieve that level.”

Mark Challberg, PhD, head of the virology branch of the National Institutes of Health, said neutralizing antibodies against poxviruses are complicated.

“While protection is certainly related to a level of neutralizing antibodies, it is by no means a 1:1 relationship,” he told CIDRAP. Challberg has studied Jynneos since it was developed after 9/11 as a monkeypox vaccine. “What you think of a vaccine based on a specific neutralizing antibody is fraught with pitfalls,” he added.

Challberg said he is currently comfortable with the path U.S. officials are taking toward intradermal dosing, adding that if he was in a high-risk group, he wouldn’t hesitate to get MVA. As for long-term protection, “we’ll have to wait and see.”

Dose economy still largely untested

Marion Koopmans, DVM, PhD, head of the Erasmus MC Department of Viroscience and one of the paper’s co-authors, said the current US strategy of using intradermal injections at one-fifth the dose of an injection standard should be tested.

“There are hypotheses that intradermal stimulates a more vigorous response,” Koopmans said. “And there are studies for other viruses that have seen such an effect, but also the other way around.”

“This is a large-scale outbreak in regions that can afford to do the proper studies to get answers to critical questions,” she said.