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

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.

Multinational monkeypox outbreak: what do we know and what should we do?

“…One vaccine (JYNNEOS™) is based on a live, attenuated vaccinia virus (Modified Vaccinia Ankara) that is unable to propagate in the body, but capable of eliciting potent immune responses. The other one is a replication-competent live vaccinia virus vaccine (ACAM2000®), meaning that the virus in the vaccine can be transmitted from recipients to unvaccinated individuals [ 13 ].…”

Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022

“…A robust antibody response following a single dose of JYNNEOS has been observed in clinical trials ( 9 ). In addition, limited data from animal model studies indicate that a single dose of JYNNEOS might provide protection for some persons against orthopoxvirus infection when administered before and closely after (1 day) viral challenge ( 10 , 11 ).…”

Monkeypox: A Contemporary Review for Healthcare Professionals

“…There are limited data on the efficacy of Jynneos in preventing MPXV in humans. Its efficacy is inferred from vaccine efficacy studies using animal models (prairie dogs and cynomolgus macaques) [ 117 , 118 ] and safety and immunogenicity studies in humans [ 119 ]. A third vaccine, Aventis Pasteur Small Pox Vaccine, is an experimental smallpox vaccine made from replication-competent Vaccinia virus, similar to ACAM2000.…”

“…ACAM2000 and Jynneos have been studied as postexposure prophylaxis (PEP) using intranasal challenge animal models [ 118 ]. Both vaccines conferred some degree of protection against monkeypox at lower inoculum doses.…”

“…Both vaccines conferred some degree of protection against monkeypox at lower inoculum doses. Administration of vaccine at 1 day postexposure was more effective than administration at 3 days postexposure for Jynneos, but ACAM2000 was similarly effective at either postexposure vaccination timepoint [ 118 ]. Vaccination of healthcare workers against monkeypox in the DRC was safely conducted as part of real-world feasiibility and immunogenicity studies with ongoing follow-up [ 120 ].…”