Immunogenic proteins and potential delivery platforms for mpox virus vaccine development: A rapid review

Abstract

Since May 2022, the mpox virus (MPXV) has spread worldwide and become a potential threat to global public health. Vaccines are important tools for preventing MPXV transmission and infection in the population. However, there are still no available potent and applicable vaccines specifically for MPXV. Herein, we highlight several potential vaccine targets for MPVX and emphasize potent immunogens, such as M1R, E8L, H3L, A29L, A35R, and B6R proteins. These proteins can be integrated into diverse vaccine platforms to elicit powerful B-cell and T-cell responses, thereby providing protective immunity against MPXV infection. Overall, research on the MPXV vaccine targets would provide valuable information for developing timely effective MPXV-specific vaccines.

Keywords: Epitopes; MPXV; Platforms; Targets; Vaccine.

Fig. 1

Genome and structure of mpox virus (MPXV). (A) The genome of MPXV (ON563414) consists of two variable regions on the left and right and a large conserved central genomic region which is delimited by ORFs C10L and A25R. The left (approximately 25 kb in size) and right (approximately 64 kb in size) variable regions encode proteins that may be associated with viral virulence and host-range factors and include a same but oppositely oriented 6438 bp sequence, called inverted terminal repeats (ITR) which are the hot spots for mutation. The viral core region (approximately 101 kb in size), which encodes essential enzymes and structural proteins, is 96.3 % identical with the corresponding part of the vaccinia virus (VACV). M1R (PDB ID: 1YPY), E8L (PDB ID: 4E9O), H3L (PDB ID: 5EJ0), A29L (PDB ID: 3VOP), A35R (PDB ID: 3K7B), B6R (no PDB ID available) proteins and their protein structures are represented. (B) MPXV is in the shape of a brick or oval. Two major forms of infectious virions of MPXV are IMV and EEV. The surface tubular proteins of virion are usually in the shape of regular 10 nm long protrusions, beneath which are envelope containing A35R and B6R proteins and membrane containing M1R, H3L, E8L, and A29L proteins. The most significant difference between IMV and EEV is that EEV has an additional envelope containing eight EEV-specific viral proteins. The core of the virus, delimited by the semipermeable shell, contains a large double-stranded linear DNA genome and enzymes. Lateral bodies are located around the core of the virus.

Fig. 2

The life cycle of MPXV. MPXV surface membrane protein (A29L) attaches to host cell surface glycosaminoglycans (GAGs). Then, the virus activates the host cell macropinocytosis for internalization. After MPXV enters the host cell, the virus begins to perform early, intermediate, and late genetic replication. As DNA synthesis proceeds, the genome is then surrounded by endoplasmic reticulum membranes as well as several early viral proteins to form a pre-replication focus. Discrete prereplication foci grow to form replication factories (RFs) that are surrounded by membranes. The viral genome is wrapped to form immature viruses with nucleoli (IVNs). Then, IVNs mature into intracellular mature virions (IMV), and IMV is encapsulated by a double membrane from the Golgi apparatus, forming an intracellular enveloped virus (IEV). IEV uses microtubules in Golgi to move from the site of membrane wrapping to the cell surface and fuse with the plasma membrane to form cell associated enveloped viruses (CEV). Then, CEV triggers host cells to form an actin tail that propels the virus out of host cells, and the virion released is called extracellular enveloped virions (EEV).

Fig. 3

Amino acid sequences of six vaccine targets TMHMM 2.0 is used to predict the transmembrane structural domain of amino acid sequences. GAGs-binding domains, B- and T-cell epitopes domain, and signaling peptides domain on amino acid sequences were shown. The N-terminal and C-terminal specific structural domains of each protein are also indicated.

Fig. 4

Different platforms based on the MPXV antigens for MPXV-specific vaccine development. Multiple platforms such as multiepitope subunit-, mRNA and DNA-, viral vector-, and nanoparticles-based platforms can be used for MPXV-specific vaccines to deliver the target proteins to elicit host robust humoral and cellular immunity.

Fig. 5

Immune response to monkeypox virus vaccination A. Vaccination with monkeypox virus-specific vaccines. B. Dendritic cells (DCs) in the lymph nodes react intracellularly to antigens presented by different types of vaccines via PRRs and load antigenic peptides via MHC. B cells recognize antigens directly and initiate humoral immune responses via BCRs and present antigenic peptide fragments to helper T cells (CD4+ T cell) via MHC class II molecules. The activation of CD4+ T cells by APCs causes them to differentiate into different subtypes, such as T follicular helper cells (Tfh cell), which also help B cells to differentiate into memory B cells and antibody-secreting plasma cells and promote the production of high-affinity antibodies. Cytotoxic T cells (CD8+ T cell) recognize antigenic peptide fragments presented by MHC class I through TCRs and trigger a cellular immune response.