Current status of next-generation vaccines against mpox virus: a scoping review

Abstract

Introduction: The mpox disease, caused by the mpox virus (MPXV), has become a rising public health issue due to its potential to cause outbreaks. Consistently, this investigation aims to evaluate the current advances in the development of novel immunotherapeutic approaches against MPXV, which are crucial for preventing and controlling mpox spread.

Methods: This scoping review was performed by analyzing the content of English-language articles published between 2018 and 2024, which reported the development of next-generation vaccines against MPXV and their assessment in animal models. Patents within the scope of this research were also included. Contrarywise, studies based solely on immunoinformatic methods, reviews, book chapters, news, and others were excluded. The literature search was executed in 11 databases, such as Scopus, MEDLINE, and PubMed.

Results: A total of 36 records (32 studies and 4 patents) were included in this review. All 32 articles contain preclinical studies with varied group sizes (4-16) in which the main animal models were BALB/c mice. Less commonly used models included CAST/Ei mice and cynomolgus macaques. Moreover, most vaccines targeted one or more MPXV antigens, such as A29L, A35R, B6R, and M1R, through active immunization (via mRNAs or recombinant antigens) or passive immunization (antibody delivery).

Conclusion: Overall, new generation vaccines might represent prospective candidates to combat the mpox health concern. Nonetheless, several of the analyzed studies possess drawbacks, including animal models with limited similarity to humans, small group sizes, and brief follow-up durations. Consequently, additional research is required to ascertain the long-term protection, efficacy, and safety of these immunotherapeutic approaches.

Keywords: antibody; immunotherapy; mRNA therapeutics; mpox virus; recombinant antigen; vaccine.

FIGURE 1

Pictorial representation of the evolution of mpox vaccine candidates across time (created with a licensed version of BioRender.com).

FIGURE 2

Flow diagram of the search methodology followed in this scoping review. The methodology was conducted following the PRISMA guidelines.

FIGURE 3

Overview of the mechanisms of new generation vaccines against MPXV. (A) mRNA and circRNA vaccines function by encoding MPXV antigens (e.g., A29L, A35R, B6R, E8L, and/or M1R), which trigger immune responses that prepare the system against the virus. (B) Recombinant protein vaccines, on the other hand, deliver specific antigens produced in expression platforms like Escherichia coli or CHO cells, directly stimulating immune responses without the need for cellular transcription. (C) mRNA-based antibody vaccines encode antibodies that target MPXV antigens, enabling the body to produce them internally and offering a faster protective alternative to conventional active immunization through the neutralization of the virus. (D) Similarly, anti-MPXV antibody vaccines work by administering antibodies produced in mammalian cells (using either recombinant or hybridoma technology), providing immediate immunity without requiring the host to produce its own antibodies (created with a licensed version of BioRender.com).

FIGURE 4

Results of the risk of bias assessment. The domains were evaluated for each included article, considering criteria for preclinical studies. Quotations extracted from the reports were included within the assessment to justify the risk assigned to each of the domains. The cells in green color represent low risk, yellow color unclear risk, and red color high risk.

FIGURE 5

Future directions for next-generation mpox vaccine development. (A) Forthcoming investigations should explore more in-depth antibody-based strategies, multivalent vaccines targeting multiple clades of MPXV, and the utilization of MPXV, rather than VACV, for challenge studies, incorporating diverse MPXV clades for comprehensive analysis. (B) The use of animal models that better replicate human disease complexity, such as non-human primates, along with the integration of data from other animal models, can support more robust analyses of mpox vaccine efficacy. (C) Ensuring adequate group sizes and avoiding over-standardization of experimental conditions will be key for validating reproducibility while standardizing factors such as lethal doses and virus administration routes tailored to the biological model is necessary. (D) Additional focus on pharmacodynamics, pharmacokinetics, safety, long-term protection, bioinformatic studies, emerging adjuvants (e.g., programable macrophage-derived vesicles) and plant-based vaccine development will also contribute to advancing mpox vaccine research (created with a licensed version of BioRender.com).