IMVAMUNE® and ACAM2000® Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model

M Shannon Keckler; Johanna S Salzer; Nishi Patel; Michael B Townsend; Yoshinori J Nakazawa; Jeffrey B Doty; Nadia F Gallardo-Romero; Panayampalli S Satheshkumar; Darin S Carroll; Kevin L Karem; Inger K Damon

doi:10.3390/vaccines8030396

IMVAMUNE^® and ACAM2000^® Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model

Vaccines (Basel). 2020 Jul 20;8(3):396. doi: 10.3390/vaccines8030396.

Authors

M Shannon Keckler^{1

2}, Johanna S Salzer^{1

3}, Nishi Patel^{1

4}, Michael B Townsend¹, Yoshinori J Nakazawa¹, Jeffrey B Doty¹, Nadia F Gallardo-Romero¹, Panayampalli S Satheshkumar¹, Darin S Carroll^{1

5}, Kevin L Karem^{1

6}, Inger K Damon¹

Affiliations

¹ Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USA.
² Clinical and Environmental Microbiology Branch, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USA.
³ Bacterial Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USA.
⁴ Respiratory Diseases Branch, Division of Bacterial Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USA.
⁵ Office of the Director, National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USA.
⁶ Office of the Director, Center for Global Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USA.

Abstract

The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today's populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 10⁴ pfu (2× LD₅₀) or 10⁶ pfu (170× LD₅₀) and vaccinated the animals with IMVAMUNE^® or ACAM2000^® either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD₅₀, but not the 170× LD₅ challenge. In the 2× LD₅₀ challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE^®, but ACAM2000^® was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented.

Keywords: monkeypox virus; postexposure vaccination; prairie dog model; smallpox vaccines.