Approaches to Next-Generation Capripoxvirus and Monkeypox Virus Vaccines

Abstract

Globally, there are two major poxvirus outbreaks: mpox, caused by the monkeypox virus, and lumpy skin disease, caused by the lumpy skin disease virus. While vaccines for both diseases exist, there is a need for improved vaccines. The original vaccines used to eradicate smallpox, which also protect from the disease now known as mpox, are no longer acceptable. This is mainly due to the risk of serious adverse events, particularly in HIV-positive people. The next-generation vaccine for mpox prevention is modified vaccinia Ankara, which does not complete the viral replication cycle in humans and, therefore, has a better safety profile. However, two modified vaccinia Ankara immunizations are needed to give good but often incomplete protection, and there are indications that the immune response will wane over time. A better vaccine that induces a long-lived response with only one immunization is desirable. Another recently available smallpox vaccine is LC16m8. While LC16m8 contains replicating vaccinia virus, it is a more attenuated vaccine than the original vaccines and has limited side effects. The commonly used lumpy skin disease vaccines are based on attenuated lumpy skin disease virus. However, an inactivated or non-infectious vaccine is desirable as the disease spreads into new territories. This article reviews novel vaccine approaches, including mRNA and subunit vaccines, to protect from poxvirus infection.

Keywords: LSDV; mpox: lumpy skin disease; poxvirus; vaccines.

Figure 1

Schematic representation of the replication cycle of Orthopoxviruses. Above, a schematic of an enveloped particle (EV). The outer membrane is represented by a red line, and the inner by a black line. The surface proteins of each membrane are indicated alongside. Below, the main steps of viral replication are indicated. The main neutralization determinants identified so far are highlighted in red, alongside the specific viral step they are involved in. Key abbreviations include MV for mature virion, IV for immature virion, IMV for intracellular mature virion, WV for wrapped virion, CEV for cell-associated virion, EEV for extracellular enveloped virion, EFC for entry fusion complex, and TGN for trans-Golgi network. With permission from Pablo Guardado-Calvo [37].