ABSTRACT
Over the past 2 years, the world has faced the impactful Coronavirus Disease-2019 (COVID-19) pandemic, with a visible shift in economy, medicine, and beyond. As of recent times, the emergence of the monkeypox (mpox) virus infections and the growing number of infected cases have raised panic and fear among people, not only due to its resemblance to the now eradicated smallpox virus, but also because another potential pandemic could have catastrophic consequences, globally. However, studies of the smallpox virus performed in the past and wisdom gained from the COVID-19 pandemic are the two most helpful tools for humanity that can prevent major outbreaks of the mpox virus, thus warding off another pandemic. Because smallpox and mpox are part of the same virus genus, the Orthopoxvirus genus, the structure and pathogenesis, as well as the transmission of both these two viruses are highly similar. Because of these similarities, antivirals and vaccines approved and licensed in the past for the smallpox virus are effective and could successfully treat and prevent an mpox virus infection. This review discusses the main components that outline this current global health issue raised by the mpox virus, by presenting it as a whole, and integrating aspects such as its structure, pathogenesis, clinical aspects, prevention, and treatment options, and how this ongoing phenomenon is being globally approached.
ABSTRACT
Increasing cases of SARS-CoV-2 breakthrough infections from immunization with current spike protein-based COVID-19 vaccines highlight the need to develop alternative vaccines using different platforms and/or antigens. In this study, we expressed SARS-CoV-2 spike and nucleocapsid proteins based on a novel vaccinia virus (VACV) ACAM2000 platform (rACAM2000). In this platform, the vaccinia virus host range and immunoregulatory gene E3L was deleted to make the virus attenuated and to enhance innate immune responses, and another host range gene, K3L, was replaced with a poxvirus ortholog gene, taterapox virus 037 (TATV037), to make virus replication competent in both hamster and human cells. Following a single intramuscular immunization, the rACAM2000 coexpressing the spike and nucleocapsid proteins induced significantly improved protection against SARS-CoV-2 challenge in comparison to rACAM2000 expressing the individual proteins in a hamster model, as shown by reduced weight loss and shorter recovery time. The protection was associated with reduced viral loads, increased neutralizing antibody titer, and reduced neutrophil-to-lymphocyte ratio. Thus, our study demonstrates that rACAM2000 expressing a combination of the spike and nucleocapsid antigens is a promising COVID-19 vaccine candidate, and further studies will investigate if the rACAM2000 vaccine candidate can induce a long-lasting immunity against infection by SARS-CoV-2 variants of concern. IMPORTANCE Continuous emergence of SARS-CoV-2 variants which cause breakthrough infection from the immunity induced by current spike protein-based COVID-19 vaccines highlights the need for new generations of vaccines that will induce long-lasting immunity against a wide range of the variants. To this end, we investigated the protective efficacy of the recombinant COVID-19 vaccine candidates based on a novel VACV ACAM2000 platform, in which an immunoregulatory gene, E3L, was deleted and both the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens were expressed. Thus, it is expected that the vaccine candidate we constructed should be more immunogenic and safer. In the initial study described in this work, we demonstrated that the vaccine candidate expressing both the S and N proteins is superior to the constructs expressing an individual protein (S or N) in protecting hamsters against SARS-CoV-2 challenge after a single-dose immunization, and further investigation against different SARS-CoV-2 variants will warrant future clinical evaluations.