FDA Approves 1st live, Non-replicating Vaccine to Prevent Smallpox & Monkeypox

Geographic Range of Monkeypox - Credit WHO

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In this year's  CDC: 8 Zoonotic Diseases Of Most Concern In The United States, Monkeypox ranks 29th; about halfway down their list.  Similarly, in 2018's WHO List Of Blueprint Priority Diseases - while Monkeypox did not make the final list (n=8) - it was mentioned as a disease to watch.

Human monkeypox was first identified in 1970 in the DRC, and since then has sparked small, sporadic outbreaks in the Congo Basin and Western Africa. It produces a remarkably `smallpox looking' illness in humans, albeit not as deadly. The CDC's Monkeypox website states:

The illness typically lasts for 2−4 weeks. In Africa, monkeypox has been shown to cause death in as many as 1 in 10 persons who contract the disease.

Human-to-human transmission is also possible.  This from the CDC’s Factsheet on Monkeypox:

The disease also can be spread from person to person, but it is much less infectious than smallpox. The virus is thought to be transmitted by large respiratory droplets during direct and prolonged face-to-face contact. In addition, monkeypox can be spread by direct contact with body fluids of an infected person or with virus-contaminated objects, such as bedding or clothing.

According to the CDC there are two distinct genetic groups (clades) of monkeypox virus—Central African and West African. West African monkeypox - which has been spreading recently in Nigeria - is associated with milder disease, fewer deaths, and limited human-to-human transmission.

Currently, there is an ongoing Monkeypox outbreak in the DRC (see WHO AFRO Outbreaks and Emergencies Bulletin).

Since the beginning of 2019, a cumulative total of 3 969 monkeypox cases, including 68 deaths (CFR 1.8%) were reported from 111 health zones in 16 provinces. In week 35 (week ending 1 September 2019), 113 cases and four deaths were reported nationally and majority of cases were reported from Kole Health zone in Sankuru

Nigeria reported its first Monkeypox outbreak in nearly 40 years in the fall of 2017, while last fall the UK saw two imported cases from Nigeria (see Eurosurveillance Rapid Comms: Two cases of Monkeypox imported to the UK) and a month later Israel: MOH Confirmed An Imported Monkeypox Case).

More recently, in May of this year Singapore's MOH announced their 1st Imported Case Of Monkeypox (ex Nigeria). Nigeria apparently continues to see sporadic transmission of the Monkeypox virus, but hasn't released an updated Sitrep since January of this year (see Monkeypox Outbreak in Nigeria for Week 5).

Routine vaccination against smallpox - which supposedly provides about 85% protection against Monkeypox - ended in the 1970s. Today more than half of the world's population is unvaccinated, and the level of protection remaining among those vaccinated 50+ years ago is highly suspect.

The world's supply of smallpox vaccine is extremely limited, and the older replicating smallpox vaccine carried some serious health risks. Despite these shortcomings it was used last year to help contain the UK's mini-outbreak (see Report: UK PHE Imports Smallpox Vaccine For HCWs Caring For Monkeypox Cases).

Given the likelihood of additional exports of the virus, and the potential for the virus to evolve into something more easily transmissible, yesterday's  announcement from the FDA that they've approved a new non-replicating Smallpox/Monkeypox vaccine is a welcome development.

This from the FDA.

FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox 

For Immediate Release: September 24, 2019

The U.S. Food and Drug Administration announced today the approval of Jynneos Smallpox and Monkeypox Vaccine, Live, Non-Replicating, for the prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. This is the only currently FDA-approved vaccine for the prevention of monkeypox disease.

“Following the global Smallpox Eradication Program, the World Health Organization certified the eradication of naturally occurring smallpox disease in 1980. Routine vaccination of the American public was stopped in 1972 after the disease was eradicated in the U.S. and, as a result, a large proportion of the U.S., as well as the global population has no immunity,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research.

“Therefore, although naturally occurring smallpox disease is no longer a global threat, the intentional release of this highly contagious virus could have a devastating effect. Today’s approval reflects the U.S. government’s commitment to preparedness through support for the development of safe and effective vaccines, therapeutics, and other medical countermeasures.”

Jynneos will be available for those determined to be at high risk of either smallpox or monkeypox infection. This vaccine is also part of the Strategic National Stockpile (SNS), the nation’s largest supply of potentially life-saving pharmaceuticals and medical supplies for use in a public health emergency that is severe enough to cause local supplies to be depleted. The availability of this vaccine in the SNS will help ensure that the vaccine is accessible in the U.S. if needed.

Smallpox, which is caused by the variola virus, emerged in human populations thousands of years ago and is a highly contagious and often fatal infectious disease. A person infected with smallpox typically develops a rash characterized by raised pocks on the face and body. The smallpox virus is spread through saliva and droplets from the respiratory tract or by direct or indirect contact with the virus as it is shed from skin lesions. The virus can also be spread through other body fluids and contaminated clothing or bed linen. If a person is infected with smallpox and they are in close contact with others, the virus can spread quickly.

Monkeypox, which does not occur naturally in the U.S., is a rare disease caused by infection with monkeypox virus, which causes symptoms similar to, but milder than, smallpox. Monkeypox begins with fever, headache, muscle aches and exhaustion and can be fatal, even though it is typically milder than smallpox. It is transmitted to people from various wild animals, such as rodents and primates. In 2003, the U.S. experienced an outbreak of monkeypox, which was the first time human monkeypox was reported outside of Africa.

Jynneos does not contain the viruses that cause smallpox or monkeypox. It is made from a vaccinia virus, a virus that is closely related to, but less harmful than, variola or monkeypox viruses and can protect against both of these diseases. Jynneos contains a modified form of the vaccinia virus called Modified Vaccinia Ankara, which does not cause disease in humans and is non-replicating, meaning it cannot reproduce in human cells.

The effectiveness of Jynneos for the prevention of smallpox was determined in a clinical study comparing the immune responses in study participants who received either Jynneos or ACAM2000, an FDA-approved vaccine for the prevention of smallpox. The study included approximately 400 healthy adults, 18 through 42 years of age who had never been vaccinated for smallpox, in which half of the study participants received two doses of Jynneos administered 28 days apart, and half received one dose of ACAM2000. The group vaccinated with Jynneos had an immune response that was not inferior to immune responses to ACAM2000. Vaccine effectiveness for the prevention of smallpox was also inferred from supportive animal studies that showed prior vaccination with Jynneos protected non-human primates who were exposed to viruses related to the smallpox virus.

The effectiveness of Jynneos for the prevention of monkeypox disease is inferred from the antibody responses in the smallpox clinical study participants and from studies in non-human primates that showed protection of animals vaccinated with Jynneos who were exposed to the monkeypox virus.

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Although monkeypox is normally restricted to small outbreaks in Africa, in 2003 we saw a rare outbreak in the United States when a Texas animal distributor imported hundreds of small animals from Ghana, which in turn infected prairie dogs that were subsequently sold to the public (see MMWR Update On Monkeypox 2003).

By the time that outbreak was quashed, the U.S. saw 37 confirmed, 12 probable, and 22 suspected human cases. Among the confirmed cases 5 were categorized as being severely ill, while 9 were hospitalized for > 48 hrs; although no patients died (cite).

This new vaccine will be incorporated into the Strategic National Stockpile (see Upcoming Webinar: The Strategic National Stockpile), which should provide a safer, and more readily available, medical countermeasure in the event that Monkeypox or Smallpox threaten again.