Progress and prospects on vaccine development against monkeypox infection

Abstract

The monkeypox virus (MPOX) is an uncommon zoonotic illness brought on by an orthopoxvirus (OPXV). MPOX can occur with symptoms similar to smallpox. Since April 25, 2023, 110 nations have reported 87,113 confirmed cases and 111 fatalities. Moreover, the outspread prevalence of MPOX in Africa and a current outbreak of MPOX in the U.S. have made it clear that naturally occurring zoonotic OPXV infections remain a public health concern. Existing vaccines, though they provide cross-protection to MPOX, are not specific for the causative virus, and their effectiveness in the light of the current multi-country outbreak is still to be verified. Furthermore, as a sequel of the eradication and cessation of smallpox vaccination for four decades, MPOX found a possibility to re-emerge, but with distinct characteristics. The World Health Organization (WHO) suggested that nations use affordable MPOX vaccines within a framework of coordinated clinical effectiveness and safety evaluations. Vaccines administered in the smallpox control program and conferred immunity against MPOX. Currently, vaccines approved by WHO for use against MPOX are replicating (ACAM2000), low replicating (LC16m8), and non-replicating (MVA-BN). Although vaccines are accessible, investigations have demonstrated that smallpox vaccination is approximately 85% efficient in inhibiting MPOX. In addition, developing new vaccine methods against MPOX can help prevent this infection. To recognize the most efficient vaccine, it is essential to assess effects, including reactogenicity, safety, cytotoxicity effect, and vaccine-associated side effects, especially for high-risk and vulnerable people. Recently, several orthopoxvirus vaccines have been produced and are being evaluated. Hence, this review aims to provide an overview of the efforts dedicated to several types of vaccine candidates with different strategies for MPOX, including inactivated, live-attenuated, virus-like particles (VLPs), recombinant protein, nucleic acid, and nanoparticle-based vaccines, which are being developed and launched.

Keywords: Immunity; Monkeypox; Nanovaccine; Nucleic acid vaccine; Vaccine.

Graphical abstract

Fig. 1

The structural features of MPOX and its structure of the extracellular enveloped and intracellular mature orthopox virion. MPOX is an enveloped ds-DNA virus that belongs to the genus OPXVs in the family Poxviridae.

Fig. 2

MPOX genome structure. There are about 197 kilobase pairs (kbp) in the MPOX genome, with the core genomic region totaling 101,476 kbp. The coding area, NR1, and NR2 sections, and inverted terminal repeats (ITR) totaling 6379 base pairs are present in both ends of the molecule [45].

Fig. 3

Schematic representation of an MPOX life cycle. Enveloped Virion (EV) enters the host cell by fusion and the mature virion (MV) by micropinocytosis or fusion.

Fig. 4

This diagram shows how MPOX infection may have an immunopathogenesis (innate immunity, adaptive immunity, and humoral immunity). The NK cell's ability to destroy virus-infected cells and release pro-inflammatory cytokines may be inhibited by MPOX. By preventing T cell receptor trans-signaling, MPOX may also obstruct the adaptive immune response [54].

Fig. 5

This illustration shows how MPOX infection may have an immunopathogenesis (innate immunity, adaptive immunity, and humoral immunity). The NK cell's ability to destroy virus-infected cells and release pro-inflammatory cytokines may be inhibited by MPOX. By preventing T cell receptor trans-signaling, MPOX may also obstruct the adaptive immune response.

Fig. 6

Infection with MPOX and several vaccination platforms (e.g., live attenuated vaccines, inactivated vaccines, protein subunit vaccines, VLP, nucleic acid vaccines, nanovaccine).

Fig. 7

In addition to facilitating effective vaccine delivery to tissues and cells, MPOX nanovaccines also allow for the simultaneous delivery of adjuvants and antigens. Furthermore, nanovaccines enable the potentiation of immunomodulation by multivalent antigens and, or adjuvants. When compared to conventional formulations, nanotechnology has the potential to increase therapeutic efficacy and change the viral vaccine market significantly.