By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has issued an emergency use authorization (EUA) for an intradermal injection of a smallpox and monkeypox vaccine.1 This vaccine is an attenuated, non-replicating orthopoxvirus from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) and grown in primary chicken embryo fibroblast cells.2 It was approved in 2019 as two 0.5 mL doses given subcutaneously (SQ) 28 days apart. The intent of the EUA is to conserve the vaccine supply by using one-fifth of the dose intradermally (ID). The lower dose, ID administration, has shown immunogenic noninferiority to the SQ route, thus expanding the U.S. vaccine supply (if fully adopted) by up to five times.3 This vaccine is marketed as Jynneos.
INDICATIONS
MVA-BN can be administered to prevent smallpox and monkeypox in adults age 18 years and older who are at high risk for contracting the infections.2
DOSAGE
The EUA recommends giving 0.1 mL ID in two doses 28 days apart.1 MVA-BN is available as 0.5 mL vials.
POTENTIAL ADVANTAGES
MVA-BN is the only available, non-replicating monkeypox vaccine. The other licensed smallpox vaccine (ACAM2000) is live vaccinia virus.4 It has been made available to prevent monkeypox under an Expanded Access — Investigational New Drug application.5 Adverse events following an ACAM2000 injection include myopericarditis/pericarditis or vaccinia virus transmission to household contacts.5 MVA-BN was found to be safe and effective in immunocompromised individuals.1
POTENTIAL DISADVANTAGES
Maximum measured local reactogenicity (erythema or induration) was significantly higher with ID injection compared to SQ administration.3 Severe local reaction (> 30 mm) was reported in 95% of ID-administered subjects vs. 58% of SQ-administered subjects. Reactogenicity lasting at least 30 days also was more frequent (67% vs. 25%). Systemic adverse reactions include muscle pain, headache, fatigue, nausea, and chills and generally are similar between ID and SQ routes.2,3 Some have reported difficulty squeezing five 0.1 mL doses from a 0.5 mL vial.
COMMENTS
The vaccine effectiveness against smallpox was based on an open-label study of the immunogenicity (geometric mean titer [GMT] of vaccinia-neutralizing antibodies against smallpox) of MVA-BN and ACAM2000.2 Noninferiority of the peak visit GMT was demonstrated compared to ACAM2000. The GMT was higher for MVA-BN vs. ACAM2000 (153 subjects vs. 84 subjects [95% CI, 133-175 vs. 95% CI, 73-97]). Evidence for comparable effectiveness of the low two-dose ID regimen was from a study of healthy subjects, which revealed immunogenicity post-peak vaccination 2 (i.e., geometric mean of peak neutralization titer) was non-inferior following the alternative regimen (n = 146) vs. the standard two-dose SQ regimen (n = 149).3 Seroconversion rates were 94.5% and 95.3%, respectively.
CLINICAL IMPLICATIONS
Monkeypox continues to spread in the United States and globally. Health and Human Services Secretary Xavier Becerra declared this a public health emergency. This included the EUA for MVA-BN, expanding the vaccine supply. There is no FDA-approved treatment for monkeypox. Tecovirimat, an antiviral against Orthopoxviruses, is approved for smallpox and has shown efficacy against monkeypox in animal models.6 As part of the public health emergency, tecovirimat has been made available to states and jurisdictions.5 Meanwhile, the FDA and CDC are focusing on expanding the vaccine supply and boosting vaccination rates for the 1.7 million Americans considered at highest risk.
REFERENCES
1. U.S. Food & Drug Administration. Monkeypox update: FDA authorizes emergency use of Jynneos vaccine to increase vaccine supply. Aug. 9, 2022.
2. Bavarian Nordic. Jynneos prescribing information. June 2021.
3. Frey SE, Wald A, Edupuganti S, et al. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects. Vaccine 2015;33:5225-5234.
4. Emergent Product Development Gaithersburg Inc. ACAM2000 prescribing information. Revised March 2018.
5. Centers for Disease Control and Prevention. ACAM2000 vaccine. Updated Aug. 9, 2022.
6. Sherwat A, Brooks JT, Birnkrant D, Kim P. Tecovirimat and the treatment of monkeypox - past, present, and future considerations. N Engl J Med 2022; Aug 3. doi: 10.1056/NEJMp2210125. [Online ahead of print].
Jynneos can be administered to prevent smallpox and monkeypox in adults age 18 years and older who are at high risk for contracting the infections.
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