1 

Paul Chaplin, Ph.D.

CEO, Bavarian Nordic A/S

Philip Heymans Alle 3

DK-2900

Denmark

August 12, 2022

Dear Dr. Chaplin: 

This is in response to your letter of August 9, 2022, regarding FDA’s emergency use authorization (EUA) 

for JYNNEOS (Modified Vaccinia Ankara-Bavaria Nordic, MVA-BN) to allow healthcare providers to use 

the vaccine by intradermal injection for individuals 18 years of age and older who are determined to be at 

high risk for monkeypox infection. This authorization also allows for use of the vaccine in individuals 

younger than 18 years of age determined to be at high risk of monkeypox infection; in these individuals 

JYNNEOS is administered by subcutaneous injection.

One of FDA’s top priorities is to address the monkeypox public health emergency as quickly as possible. 

In recent weeks, the monkeypox virus has continued to spread at a rapid rate that has made it clear our 

current vaccine supply will not meet the current demand. As of August 11, 2022, there have been 

10,768 confirmed cases of monkeypox in the United States. The continued spread of monkeypox has 

necessitated that FDA vigorously explore all available vaccine options to provide protection for the 

population at risk.. 

As you are aware, the supply of JYNNEOS available for distribution through the end of this year is 

estimated to only be sufficient to immunize half of the individuals at highest risk for monkeypox. In the 

absence of an adequate supply, we have evaluated the use of alternative vaccines and potential ways to 

maximize the number of individuals immunized with the available vaccine supply. Use of alternative 

vaccines was determined to be either impractical or inadvisable at this time. 

More specifically, ACAM2000 may not be appropriate now for a potentially immunocompromised 

population. The local and systemic toxicities of this vaccine may not be considered to be acceptable for 

the prevention of monkeypox. Consideration was also given to delaying second vaccine doses by 3 to 6 

months. However, following careful review of the available animal data with JYNNEOS, and 

acknowledging the absence of data applicable to this situation, this option was determined to be 

inadvisable, particularly because it might both be insufficiently protective while at the same time providing

individuals with a false sense of reassurance that they were protected against monkeypox when the actual 

level of protection would be unknown and quite possibly inadequate.

The other options examined looked at approaches that could potentially more effectively provoke an 

immune response, such as intradermal administration. As you are aware, Stickl and colleagues deployed 

a Modified Vaccinia Ankara (MVA) in Germany by the intradermal route, treating both children and adults 

(Stickl HA, Preventive Medicine, 1974; 3:97-101, among others) Since that time intradermal MVA or 

modified MVA have been used intradermally in several small studies performed in both immunocompetent 

and immunocompromised individuals (including those with human immunodeficiency virus, HIV).

As you were a co-author (Frey et al, Vaccine, 2015; 33:5225-5234), you are also aware that the MVA 

vaccine was evaluated as a two-dose series given intradermally compared to subcutaneously in a study 

sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). Individuals who received 
2 

the vaccine intradermally received a lower volume (one fifth) than individuals who received the vaccine 

subcutaneously. The results of this study demonstrated that intradermal administration produced a very 

similar immune response to subcutaneous (SC) administration. Administration by the intradermal (ID) 

route did result in more redness, firmness, itchiness and swelling at the injection site, but less pain, and 

these side effects were manageable. Of note, the side effect profile reported with intradermal 

administration if JYNNEOS in the NIAID study closely mirrored the side effect profile described initially by 

Stickl and colleagues (redness and occasional nodularity at the injection).

Based on a careful review of the clinical study report from the NIAID trial and the totality of available 

evidence in the literature, and considering all available options, FDA determined that the known and 

potential benefits of the use of intradermal JYNNEOS outweighed the known and potential risks for 

individuals determined to be at high risk of infection from monkeypox. FDA sought input from others from 

across academia and the US government and considered all available information prior to making this 

decision. We refer you to FDA’s posted Decision Memorandum for additional information on the 

authorization. 

In your letter, you posed several questions regarding ID administration of JYNNEOS under the EUA. Your 

questions are copied below followed by FDA’s responses:

How long do we have to use the 5 doses per vial?

We understand this question to be how much time can elapse between withdrawing the first dose until 

administering the 5th dose in each vial. After the vial is punctured and a dose is withdrawn, if it is not 

used in its entirety, it should be stored at +2°C to +8°C (+36°F to +46°F) and discarded within 8 hours of 

the first puncture. The FDA’s decision is based on stability data submitted by Bavarian Nordic to the 

approved JYNNEOS Biologics License Application (BLA) and its extensive experience with similar biologic 

products.

Is 0.1mL appropriate for both PrEP and PEP?

Yes, this dose is appropriate for individuals who are taking PrEP or PEP. The Fact Sheet for Healthcare 

Providers Administering Vaccine notes that Immunocompromised persons, including those receiving 

immunosuppressive therapy, may have a diminished immune response to JYNNEOS.

What gauge needle should be used?

A 27-gauge needle should be used as is typically used for intradermal injection. CDC has posted 

instructions for intradermal administration of JYNNEOS on its website.

How to handle misadministration?

CDC has posted clinical considerations on the website that outline how healthcare providers should 

handle dosing or administration errors, including how to handle if the vaccine is given in the wrong site, 

route, dose, or interval. We refer you to CDC’s website for information and reporting.

In summary, we certainly appreciate your concerns regarding the potential for reactogenicity associated 

with ID administration of JYNNEOS. The agency’s authorization of the vaccine for emergency use by the 

intradermal route took this into consideration as part of our evaluation. However, the agency has made its 

determination with confidence that the safety and efficacy profile of the vaccine will be maintained. Use of 
3 

the intradermal regimen will allow us to increase the number of available doses by up to five-fold, allowing 

more individuals who want to be vaccinated against monkeypox to receive the vaccine to address the 

current outbreak in the United States. The additional doses provided by using this route of administration

will allow us to address the increasing rate of spread of the virus in the United States while providing 

protection to a broader population. 

Thank you for contacting us with your concerns.

Sincerely,

Robert Califf, MD

Commissioner of Food and Drugs

Peter Marks, MD, PhD

Director, Center for Biologics Evaluation and Research