Monkeypox: The vaccine landscape
Unlike COVID-19 vaccine, the world is already equipped with a vaccine in the form of the smallpox vaccine, against the related smallpox virus, which is believed to be around 85% effective against monkeypox.
Since May 13, monkeypox has been reported to WHO from 23 member states that are not endemic for monkeypox virus. The vast majority of reported cases so far have no established travel links to an endemic area, as had previously been the case for isolated cases in the past. As of Sunday (May 26), a total of 257 laboratory confirmed cases and around 120 suspected cases had been reported to the WHO: with the most confirmed cases in Portugal (49), Canada (26) and the US (10). No deaths have been reported.
Smallpox vaccine
Experts agree that monkeypox is not likely to be the next pandemic, given the virus does not spread as easily as SARS-CoV-2. However, there is still interest in vaccines to protect vulnerable people.
Because the monkeypox virus is closely related to the virus that causes smallpox, the smallpox vaccine can protect against monkeypox. While smallpox was officially declared eradicated in 1980, the vaccine remaining in production for stockpiling against potential outbreaks or biological threats.
While the WHO confirms there is currently no need for mass vaccination against monkeypox, it suggests targeted vaccination where available for close contacts of people infected.
Unlike many other vaccines, the smallpox vaccine can be administered after exposure to the monkeypox virus, although the CDC recommends that this is done within four days.
In the US, ACAM200 (produced by Emergent Biosolutions) and Jynneos (Bavarian Nordic) are currently licensed to prevent smallpox; with Jynneos also licensed specifically to prevent monkeypox.
The US’ Strategic National Stockpile includes the smallpox vaccine. It currently has around 1,000 doses of the two-dose Jynneos vaccine available, with the CDC promising that the stock will be ramped up over the coming weeks. It also has more than 100 million doses of ACAM2000, according to government officials.
"Because monkeypox virus is closely related to the virus that causes smallpox, the smallpox vaccine can protect people from getting monkeypox. Past data from Africa suggests that the smallpox vaccine is at least 85% effective in preventing monkeypox. The effectiveness of Jynneos against monkeypox was concluded from a clinical study on the immunogenicity of Jynneos and efficacy data from animal studies.
"Smallpox & monkeypox vaccines are effective at protecting people against monkeypox when given before exposure. Experts also believe that vaccination after exposure may help prevent the disease or make it less severe."
- CDC
Vaccine producers see increased interest
Earlier this week, Bavarian Nordic announced it had signed multiple deals with governments for its two-dose smallpox vaccine: although it did not disclose the countries or quantities covered. Deliveries are set to begin immediately.
The vaccine is produced at Bavarian Nordic's facility in Kvistgaard in Denmark: which to date has already produced 28 million doses for the US Strategic National Stockpile.
Emergent Biosolutions confirmed to BioPharma-Reporter that it has received interest in its vaccine, although was not able to release any details. It notes that it has historically sold and distributed of ACAM200 doses to allied governments and other stakeholders. The company currently has the capacity to produce around 18 million doses a year.
In the US, a third investigational vaccine, Aventis Pasteur Smallpox Vaccine, is also stockpiled in the eventuality it would be used against smallpox under a EUA if stock of other vaccines is depleted.
Meanwhile, Emergent Biosolutions announced earlier this month that it will acquire the small molecule smallpox oral antiviral Tembexa (brincidofovir) from Chimerix: which became the first antiviral approved by the US FDA for all age groups for the treatment of smallpox last June.
Other potential treatment options include cidofovir and brincidofovir although the CDC notes that data is not available on these as a treatment against monkeypox.
European response
The first European case of monkeypox was confirmed on May 7, and has since spread across European countries. Germany is one of the countries understood to have made a deal with Bavarian Nordic: in this case for 40,000 doses.
Unlike in the US, Jynneos (which contains a live modified form of vaccinia Ankara) is approved in Europe only for the smallpox indication - where it is called Imvanex - but has previously been provided for off-label use in response to monkeypox cases.
Meanwhile, the European Union is working on a common purchasing agreement for vaccines and antivirals against monkeypox, with a broad consensus reached in principle by member states, Reuters reported on Friday.
And the EU is in talks to buy Imvanex from Bavarian Nordic as well as the antiviral tecovirimat from SIGA Technologies, added the news agency.
A race to create a monkey-pox specific vaccine?
Moderna has announced via Twitter that it was investigating potential monkeypox vaccines at a preclinical level, although has released little further information about the vaccine or potential timelines for development.
Underscoring this commitment, and as #monkeypox is of global public health importance as identified by the @WHO, we are investigating potential monkeypox vaccines at a preclinical level. pic.twitter.com/4VfLrxybNn
— Moderna (@moderna_tx) May 23, 2022
Meanwhile, Tonix Pharmaceuticals yesterday announced that the U.S. Patent and Trademark Office (USPTO) has issued a patent to the company for its vaccine candidate TNX-801, a smallpox and monkeypox vaccine.
The patent, entitled ‘Synthetic Chimeric Poxviruses’ includes claims covering synthetic horsepox virus, the basis for the TNX-801 vaccine, and for the company’s Recombinant Pox Virus (RPV) platform to protect against other pathogens, including SARS-CoV-2.
This patent is expected to provide New York headquartered Tonix with U.S. market exclusivity until 2037, excluding any possible patent term extensions or patent term adjustments.
TNX-801 is a horsepox-based live virus vaccine currently in development to protect against monkeypox and smallpox. “Horsepox was one of the first few viruses ever generated by synthetic biology and remains among the largest,” said Seth Lederman, M.D., CEO of Tonix Pharmaceuticals. “As we prepare to advance horsepox-based live virus vaccines into clinical development, we are excited to have this new patent as an important element of our patent estate.”
Tonix has previously reported positive data from a monkeypox challenge study in non-human primates.
Creating vaccines that can act against future virus threats
For Dr Richard Hatchett, CEO of the Coalition for Epidemic Preparedness Innovations (CEPI), the existence of the smallpox vaccine – which has now turned into a ready-made vaccine against monkeypox – is further proof of the need to create broad vaccines that can be quickly adapted against any future threats.
He highlights the organisation's focus on a ‘prototypic-vaccine approach’, where existing work in vaccine development can be used against pathogens from an entire genus of viruses.
“The response to smallpox proves that it is possible to develop vaccines against viral threats that harbour the worst traits of a viral genus or family and thereby get a significant head start on protecting against other related threats. In fact, the smallpox vaccine as a prototype vaccine gives more than a head start; it also provides protection against all other known orthopoxviruses, including monkeypox.”
Going further, CEPI believes this prototypic-vaccine approach should be taken a step further and applied to the 25 or so viral families known to infect humans.
It is already coordinating such a response to SARS-CoV-2 variants and a wider all-in-one betacoronavirus shot, with nine projects already under way.
“Orthopoxvirus and betacoronavirus vaccines would form an important component of CEPI’s planned ‘library’ of vaccine candidates—a core part of its $3.5 billion pandemic preparedness plan—which are ready to be pulled off the shelf and—if needed—swiftly adapted next time an unknown pathogen (also referred to as Disease X) emerges. By having such a library at our disposal, the world wouldn’t lose valuable time creating a new vaccine from scratch when a new viral threat is already upon us.
“At CEPI, we’re prioritising the development of vaccine libraries for up to 10 virus families that pose the greatest risk to public health. For each virus family selected, we’ll create vaccine candidates for as many as 10 to 15 different viruses depending on the complexity of the family. Our aim is to establish clinical proof of concept for vaccine libraries against multiple virus families over the next five years.”
