Vaccine Targets Research Articles

Targeting Plasmodium falciparum chondroitin sulfate a ligand: A highly conserved malaria antigen with potential for pregnancy-associated malaria vaccine development

Background Pregnant women in malaria-endemic regions exhibit heightened susceptibility to Plasmodium falciparum infection due to accumulation of infected red blood cells (iRBCs) in the placenta. This is aided by the variant antigen 2 chondroitin sulfate A (VAR2CSA) protein which remains a target for pregnancy-associated malaria (PAM) vaccine studies. However, polymorphism in this antigen presents a significant challenge in developing broadly efficacious vaccines. This study explored PfCSA-L, a protein co-expressed and co-localized with VAR2CSA, as a potential alternative vaccine target due to its hypothesized role in PAM pathogenesis. Methods Sera and dried blood spots were collected from pregnant women attending antenatal care clinic at Webuye County Hospital, Western Kenya. P. falciparum infection status was confirmed by PCR. Recombinant PfCSA-L, expressed using a eukaryotic wheat germ cell-free system (WGCFS), was used to assess IgG antibody responses via ELISA. Results We observed a statistically significant increase in IgG levels as gestation advanced, suggesting potential exposure-driven antibody maturation against PfCSA-L. Primigravida women exhibited a trend toward higher anti-PfCSA-L antibody levels compared to multigravida during the second visit, possibly reflecting a more vigorous immune response during the first pregnancy. Genetic analysis of field parasite isolates revealed a high conservation of PfCSA-L at both DNA and protein levels. B-cell epitope prediction identified potential targets on the PfCSA-L surface within the conserved region. Conclusion These findings, coupled with the observed IgG response, further positions PfCSA-L as a promising vaccine candidate for PAM. However, further investigations are warranted to elucidate the functional role of anti-PfCSA-L antibodies and definitively validate PfCSA-L and/or the identified epitopes as potential PAM vaccine targets.

A low pre-existing anti-NS1 humoral immunity to DENV is associated with microcephaly development after gestational ZIKV exposure.

Gestational Zika virus (ZIKV) infection is associated with the development of congenital Zika syndrome (CZS), which includes microcephaly and fetal demise. The magnitude and quality of orthoflavivirus-specific humoral immunity have been previously linked to the development of CZS. However, the role of ZIKV NS1-specific humoral immunity in mothers and children with prenatal ZIKV exposure and CZS remains undefined. In addition, considering that most of the at-risk population lives in dengue virus (DENV)-endemic areas, it is not clear what is the association between pre-existing DENV NS1-specific humoral immunity and CZS. Here, we studied 328 mothers and children with a clinical diagnosis and seropositivity for ZIKV infection during pregnancy, included during the 2015-2016 ZIKV epidemic in Colombia. We also performed clinical evaluation and pediatric neurological follow-up. The relative levels of circulating NS1-specific IgM and IgG against ZIKV and DENV were evaluated in mothers and children, and the association with the development of microcephaly was analyzed. DENV and ZIKV IgG-NS1 antibodies in pregnant women were placentally transferred, and this passage and its duration in children depended on the maternal levels of the antibodies. We reported that higher concentrations of pre-existing DENV, but not ZIKV IgG-NS1 antibodies, were associated with a reduced risk of CZS-related microcephaly. Also, we observed that the IgM-NS1 response in infants is long-term and has a minor association with poor outcomes. The development of microcephaly in children prenatally exposed to ZIKV is associated with low plasma levels of placentally transferred, pre-existing DENV IgG-NS1 antibodies. These data are compatible with a protective role of anti-NS1 IgG antibodies against ZIKV infection during pregnancy and highlight the promising role of NS1 as an orthoflavivirus vaccine target in high-risk populations.

Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases.

The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface. The cell lines are barcoded with fluorescent proteins, enabling high-throughput, 16-plex analyses of antibody binding with commonly available flow cytometers. The cell lines were at least as efficient as a Luminex multiplex binding assay at identifying NA antibodies from a library of unselected clonal IgGs derived from human memory B cells. The membrane-anchored NAs are catalytically active and are compatible with established small-molecule catalytic activity assays. NA-expressing K530 cell lines therefore represent a useful tool for studying NA immunity and evaluating influenza vaccine efficacy.

Subunit protein CD40.SARS.CoV2 vaccine induces SARS-CoV-2-specific stem cell-like memory CD8+ T cells

Ideally, vaccination should induce protective long-lived humoral and cellular immunity. Current licensed COVID-19 mRNA vaccines focused on the spike (S) region induce neutralizing antibodies that rapidly wane. Herein, we show that a subunit vaccine (CD40.CoV2) targeting spike and nucleocapsid antigens to CD40-expressing cells elicits broad specific human (hu)Th1 CD4+ and CD8+ T cells in humanized mice. CD40.CoV2 vaccination selectively enriched long-lived spike- and nucleocapsid-specific CD8+ progenitors with stem-cell-like memory (Tscm) properties, whereas mRNA BNT162b2 induced effector memory CD8+ T cells. CD8+ Tscm cells produced IFNγ and TNF upon antigenic restimulation and showed a high proliferation rate. We demonstrate that CD40 activation is specifically required for the generation of huCD8+ Tscm cells. These results support the development of a CD40-vaccine platform capable of eliciting long-lasting T-cell immunity. This work was supported by Inserm, Université Paris-Est Créteil, and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR.

Monkeypox: A comprehensive review on mutation, transmission, pathophysiology, and therapeutics.

Monkeypox virus (MPXV) is the causative agent of the monkeypox (Mpox) disease, belongs to the Orthopoxvirus genus of the Poxviridae family. Due to the recent re-emergence of Mpox in 2024, this is the second time when the World Health Organization (WHO) declared Mpox as a Public Health Emergency of International Concern (PHEIC). This review intends to offer an in-depth analysis of Mpox, including its key characteristics, epidemiological, mutation, pathophysiology, transmission, and therapeutics. The infection of MPXV is a lethal threat to children, pregnant women, and immunocompromised individuals. However, we can prevent the infection by proper precautions including hygiene practices and minimizing exposure to infected individuals or animals. Multivalent mRNA vaccines, antibody-based immunotherapy, and combination drug therapies have all shown significant effectiveness in treating Mpox infection. In addition to addressing antivirals and drug resistance, the review also explores potential targets for vaccine and drug development, as well as the use of animal models for studying MPXV. Because of multiple mutational events, Mpox began exhibiting drug resistance. Overall, this review will contribute significantly to advancing the development of new vaccines and drug options for combating emerging Mpox.

In silico prediction and experimental evaluation of LIP3228 of pathogenic Leptospira as a potential subunit vaccine target against leptospirosis.

A protein subunit vaccine comprising conserved surface-exposed outer membrane proteins (SE-OMPs) is considered a promising platform for leptospirosis vaccine. The search for novel vaccine candidates that confer high protective efficacy against leptospirosis is ongoing. The LIP3228 protein was previously identified as a conserved and abundant SE-OMP with the potential to serve as an effective vaccine candidate. However, it is crucial to explore the immunological properties of this vaccine antigen before proceeding with animal experiments. This study aimed to assess the immunological characteristics of LIP3228 through in silico prediction and to validate its immunogenicity and protective efficacy in a hamster model of acute leptospirosis. The LIP3228 vaccine candidate was predicted in silico to be immunogenic, with strong binding B-cell and T-cell epitopes. In the immune simulator, it demonstrated stable interactions with Toll-like receptors 2 (TLR2) and 4 (TLR4) and induced immune responses, potentially stimulating host immune responses in vivo. The animal experiment showed that immunization with recombinant LIP3228 protein, formulated with AddaVax adjuvant, induced high and specific IgG responses in hamsters, with IgG2 being the predominant subclass. Although no significant improvement in survival was observed compared to the negative control after a homologous challenge with virulent leptospires, the vaccinated hamsters showed a reduction in histopathological changes and severity of lesions in target organs compared to unvaccinated hamsters. These results suggest that the immunoinformatic prediction is effective in predicting immunogenicity but not protective efficacy. Therefore, LIP3228 could be considered a potential vaccine candidate for mitigating severe tissue damage. These findings may have significant implications for the development of subunit vaccines in the future.

Immunoinformatics design of a novel multiepitope vaccine candidate against non-typhoidal salmonellosis caused by Salmonella Kentucky using outer membrane proteins A, C, and F.

The global public health risk posed by Salmonella Kentucky (S. Kentucky) is rising, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans. In this study, we used a bioinformatics approach to develop a peptide-based vaccine targeting epitopes from the outer membrane proteins A, C, and F of S. Kentucky. Additionally, we employed flagellin protein (fliC) from Salmonella Typhimurium (S. Typhimurium) as an adjuvant to enhance the vaccine's effectiveness. Through this approach, we identified 14 CD8+ and 7 CD4+ T-cell epitopes, which are predicted to be restricted by various MHC class I and MHC class II alleles. The predicted epitopes are expected to achieve a population coverage of 94.91% when used in vaccine formulations. Furthermore, we identified seven highly immunogenic linear B-cell epitopes and three conformational B-cell epitopes. These T-cell and B-cell epitopes were then linked using appropriate linkers to create a multi-epitope vaccine (MEV). To boost the immunogenicity of the peptide construct, fliC from S. Typhimurium was included at the N-terminal. The resulting MEV construct demonstrated high structural quality and favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, and 5, followed by molecular dynamic simulations, suggested that the vaccine-receptor complexes are energetically feasible, stable, and robust. Immune simulation results showed that the MEV elicited significant responses, including IgG, IgM, CD8+ T-cells, CD4+ T-cells, and various cytokines (IFN-γ, TGF-β, IL-2, IL-10, and IL-12), along with a noticeable reduction in antigen levels. Despite these promising in-silico findings, further validation through preclinical and clinical trials is required to confirm the vaccine's efficacy and safety.

Engineering a Novel T‐Cell Epitope‐Based Vaccine Targeting PRAME in Cancer Immunotherapy

ABSTRACTPRAME, a cancer/testis antigen, is often expressed abnormally in various cancers, making it a hopeful candidate for cancer immunotherapy. This study aimed to create a vaccine targeting PRAME using immunoinformatics methods. The PRAME protein sequence was obtained from UniProtKB, and a TLR4 agonist sequence from Mycobacterium tuberculosis was included as an adjuvant. Potential T‐cell epitopes were forecasted using the IEDB server and assessed for their antigenicity, lack of allergenicity, and binding affinities to human and murine MHC molecules. Selected epitopes were then combined into a multi‐epitope structure using suitable linkers. The vaccine's physical and chemical properties, 3D structure, and interaction with TLR4 were examined through computational analyses. Five promising MHC‐I and five MHC‐II epitopes from PRAME were pinpointed and incorporated into the multi‐epitope vaccine and the TLR4 agonist adjuvant. The vaccine displayed advantageous biochemical traits, including high stability, solubility, and antigenicity. Molecular docking simulations showcased a steady interaction between the vaccine and TLR4, with a binding energy of −250.5 kcal/mol. Molecular dynamics analyses confirmed the structural stability and minimal distortion of the vaccine‐TLR4 complex. This study introduces a fresh approach to vaccine design targeting PRAME, a cancer‐related antigen. The vaccine structure exhibits promising physical, chemical, and immunological characteristics, suggesting its potential to trigger robust cellular and humoral immune responses against PRAME‐positive cancers.

Modeling the potential public health and economic impact of different COVID-19 booster dose vaccination strategies with an adapted vaccine in the United Kingdom

ABSTRACT Background Updating vaccines is essential for combatting emerging coronavirus disease 2019 (COVID-19) variants. This study assessed the public health and economic impact of a booster dose of an adapted vaccine in the United Kingdom (UK). Methods A Markov-decision tree model estimated the outcomes of vaccination strategies targeting various age and risk groups in the UK. Age-specific data derived from published sources were used. The model estimated case numbers, deaths, hospitalizations, medical costs, and societal costs. Scenario analyses were conducted to explore uncertainty. Results Vaccination targeting individuals aged ≥ 65 years and the high-risk population aged 12–64 years was estimated to avert 701,549 symptomatic cases, 5,599 deaths, 18,086 hospitalizations, 56,326 post-COVID condition cases, and 38,263 lost quality-adjusted life years (QALYs), translating into direct and societal cost savings of £112,174,054 and £542,758,682, respectively. The estimated economically justifiable price at willingness-to-pay thresholds of £20,000 and £30,000 per QALY was £43 and £61, respectively, from the payer perspective and £64 and £82, respectively, from the societal perspective. Expanding to additional age groups improved the public health impact. Conclusions Targeting individuals aged ≥ 65 years and those aged 12–64 years at high risk yields public health gains, but expansion to additional age groups provides additional gains.

Impact of the Pentavalent Meningococcal Conjugate Vaccine(NmCV-5) Targeting Serogroups A,C,Y,W, and X on the Sub-Saharan Africa Region

Meningococcal disease poses a considerable public health burden in sub-Saharan Africa (SSA), particularly in the "meningitis belt". Although the rollout of the serogroup A meningococcal vaccine (MenAfriVac) has effectively contributed to a significant reduction in the incidence of group A meningitis, serogroups C, W, Y, and X are experiencing rising infection rates, highlighting the urgent need for new vaccines to address the threat posed by non-serogroup A Neisseria meningitidis. Considering this, Serum Institute of India Pvt Ltd., in partnership with PATH, developed a pentavalent conjugate vaccine (NmCV-5) containing capsular polysaccharides of meningococcal serogroups: A, C, W, X and Y, conjugated to a protein carrier, tetanus toxoid. In this paper, the epidemic trend of meningococcal and the development of NmCV-5 vaccine in SSA were analyzed by literature review. It has been shown that the NmCV-5 vaccine demonstrated good safety and immunogenicity against all serogars in clinical trials, especially significant protection against Neisseria meningitidis serogroup X. The single-dose schedule of the vaccine also improves roll-out feasibility in resource-limited Settings. However, the rollout of the vaccine still faces challenges such as poor infrastructure and insufficient public awareness.

Insights into ecology, pathogenesis, and biofilm formation of Enterococcus faecalis from functional genomics.

SUMMARYEnterococcus faecalis is a significant resident of the gastrointestinal tract of most animals, including humans. Although generally non-pathogenic in healthy hosts, this microbe is adept at the exploitation of compromises in host immune functions, resulting in life-threatening opportunistic infections whose treatments are complicated by a high degree of intrinsic and acquired resistance to antimicrobial chemotherapy. Historically, progress in enterococcal research was limited by a lack of experimental models that replicate natural infection pathways and the relevance of in vitro studies to the natural biology of the organism. In this review, we summarize the history of enterococcal research during the 20th and early 21st centuries and describe more recent genetic and genomic tools and screens developed to address challenges in the field. We also describe how the results of recent studies reveal the importance of previously uncharacterized enterococcal genes, and we provide examples of interesting determinants that have emerged as important contributors to enterococcal biology. These factors may also serve as targets for future vaccines and chemotherapeutic agents to combat life-threatening hospital infections.

HLA-E/Mtb specific CD4+ and CD8+ T cells have a memory phenotype in individuals with TB infection.

Tuberculosis (TB) is the deadliest infectious disease worldwide and novel vaccines are urgently needed. HLA-E is a virtually monomorphic antigen presentation molecule and is not downregulated upon HIV co-infection. HLA-E restricted Mtb specific CD8+ T cells are present in the circulation of individuals with active TB (aTB) and Mtb infection (TBI) with or without HIV co-infection, making HLA-E restricted T cells interesting vaccination targets for TB. Here, we performed in-depth phenotyping of HLA-E/Mtb specific and total T cell populations in individuals with TBI and in individuals with aTB or TBI and HIV using HLA-E/Mtb tetramers. We show that HIV co-infection is the main driver in changing the memory distribution of HLA-E/Mtb specific CD4+ and CD8+ T cell subsets. HLA-E/Mtb specific CD4+ and CD8+ T cells were found to circulate with comparable frequencies in all individuals and displayed expression of KLRG1, PD-1 and 2B4 similar to that of total T cells. The presence of HLA-E/Mtb specific T cells in individuals with aTB and TBI highlights the potential of HLA-E as a vaccine target for TB.

Immunoinformatics-driven design and computational analysis of a multiepitope vaccine targeting uropathogenic Escherichia coli

Immunoinformatics-driven design and computational analysis of a multiepitope vaccine targeting uropathogenic Escherichia coli

Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer

Endometrial cancer (EC) with Mismatch Repair deficiency (MMRd) is characterized by the accumulation of insertions/deletions at microsatellite sites. These mutations lead to the synthesis of frameshift peptides (FSPs) that represent tumor-specific neoantigens (nAg) proved to be shared across patients/tumors with MMRd. In this study, we explored the feasibility of a nAg-based cancer vaccination design in EC with MMRd. We adopted a whole exome sequencing approach and ad hoc bioinformatics pipelines to characterize FSPs in 35 patients with EC. A mean of 146 mutated mononucleotide repeats (MNRs) was identified with enrichment in the patients’ group with MLH1 impairment. A high coverage emerged from the comparative analysis of the EC FSPs with the content of the previously validated NOUS-209 vaccine. We obtained pieces of evidence of FSPs translation as expressed proteins from Ribo-seq, supporting the potential as the target of vaccination. The development of a nAgs-based vaccine strategy in MMRd EC may be further explored.

Determining the intention of receiving the influenza vaccine: a cross-sectional survey among international and domestic college students in the USA

ObjectiveVaccination is the most effective strategy for preventing infectious diseases, yet it is underused in young adults. College students are important targets for the influenza vaccine given this population’s low...

Immunopeptidomic MHC-I profiling and immunogenicity testing identifies Tcj2 as a new Chagas disease mRNA vaccine candidate.

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an array of unique peptides that could be traced back to 17 distinct T. cruzi proteins. Notably, six peptides were derived from Tcj2, a trypanosome chaperone protein and member of the DnaJ (heat shock protein 40) family, showcasing its potential as a viable candidate vaccine antigen with cytotoxic T cell inducing capacity. Upon testing Tcj2 as an mRNA vaccine candidate in mice, we observed a strong memory cytotoxic CD8+ T cell response along with a Th1-skewed humoral antibody response. In vitro co-cultures of T. cruzi infected cells with splenocytes of Tcj2-immunized mice restricted the replication of T. cruzi, demonstrating the protective potential of Tcj2 as a vaccine target. Moreover, antisera from Tcj2-vaccinated mice displayed no cross-reactivity with DnaJ in lysates from mouse and human indicating a decreased likelihood of triggering autoimmune reactions. Our findings highlight how immunopeptidomics can identify new vaccine targets for Chagas disease, with Tcj2 emerging as a promising new mRNA vaccine candidate.

Designing and comparative analysis of anti-oxidant and heat shock proteins based multi-epitopic filarial vaccines

BackgroundLymphatic Filariasis (LF) is a neglected tropical disease affecting more than 882 million people in 44 countries of the world. A multi-epitope prophylactic/therapeutic vaccination targeting filarial defense proteins would be invaluable to achieve the current LF elimination goal.MethodTwo groups of proteins, namely Anti-oxidant (AO) and Heat shock proteins (HSPs), have been implicated in the effective survival of the filarial parasites in their hosts. Several B-cell, CTL, and T-helper epitopes were predicted from the three anti-oxidant proteins GST, GPx, and SOD. Likewise, epitopes were also predicted for HSP110, HSP90, and HSP70. Among the predicted epitopes, screening was applied to include only non-allergenic, non-toxic epitopes to construct two MEVs, PVAO and PVHSP. The epitopes for each group of proteins were connected to each other by the inclusion of suitable linkers and an adjuvant. The 3D models for PVAO and PVHSP were predicted, and validated, followed by prediction of physicochemical properties using bioinformatics tools. The binding free energy of PVAO and PVHSP with Toll like Receptors (TLR) TLR1/2, TLR4, TLR5, TLR6, and TLR9 was calculated with HawkDock. The immunogenicity of both the MEVs were assessed by Immune simulation after which codon adaptation and in-silico cloning were carried out.ResultsConservation of the selected AOs and HSPs in other parasitic nematode species suggested that both the generated chimera could be helpful in cross-protection too. The 3D models of both MEVs contained more than 97% residues in allowed regions, as predicted by PROCHECK server. High MMGBSA and docking scores were obtained between MEVs and TLR4, TLR1/2, TLR6, and TLR9. Molecular dynamics simulation confirmed the stability of candidate vaccines in dynamic conditions present in the biological systems. The in-silico immune simulation indicated significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses following immunization with PVAO and PVHSP.ConclusionThe immunoinformatics approaches used in this study confirmed that, the designed vaccines are capable of eliciting sustained immunity against LF, however, additional in-vivo studies would be required to confirm their efficacy. Furthermore, by employing multi-epitope structures and constructing two different cocktail vaccines for LF, this study can form an important milestone in the development of future LF vaccine/s.

Protease shaving of Mycobacterium tuberculosis facilitates vaccine antigen discovery and delivery of novel cargoes to the Mtb surface.

Tuberculosis (TB) is the leading cause of infectious disease death and lacks a vaccine capable of protecting adults from pulmonary TB. The bacterial surface is a critical interface that shapes host-pathogen interactions. Several knowledge gaps persist in our understanding of Mycobacterium tuberculosis (Mtb)-host interactions that may be addressed by an improved understanding of the Mtb surface proteome, including the identification of novel vaccine targets as well as developing new approaches to interrogate host-pathogen interactions. Here, we sought to expand our understanding of the Mtb surface proteome in service of these knowledge gaps by adapting protease shaving protocols for multiplexed quantitative mass spectrometry. Pairing quantitative mass spectrometry with the construction of validation strains, we revealed several novel Mtb proteins on the Mtb surface largely derived from the PE/PPE class of Mtb proteins, including PPE18, a component of a leading Mtb vaccine candidate. We next exploited the localization of PPE18 to decorate the Mtb surface with heterologous proteins. Together, these studies reveal potential novel targets for new Mtb vaccines as well as facilitate new approaches to study difficult-to-study cellular compartments during bacterial growth and infection.IMPORTANCEThe surface of a bacterial pathogen is a critical interface between the bacterium and the immune system. A better understanding of this interface would facilitate the discovery of new vaccine targets, new virulence proteins, and enable new technologies that modify the bacterial surface. In this study, we established a multiplexed and quantitative biochemical strategy to study the surface of Mycobacterium tuberculosis (Mtb) and identified new vaccine targets. We furthermore established design rules for new technologies aimed at modifying the composition of the bacterial surface. Specifically, we achieved a biological milestone that has not been rigorously reported previously, which is the successful modification of the Mtb surface with a non-native protein.

Immunoinformatics approach: Developing a multi-epitope vaccine with novel carriers targeting monkeypox virus.

Since May 2022, the global spread of monkeypox virus (MPXV) has presented a significant threat to public health. Despite this, there are limited preventive measures available. In this study, different computational tools were employed to design a multi-epitope vaccine targeting MPXV. Three key MPXV proteins, M1R, B6R, and F3L, were chosen for epitope selection, guided by bioinformatic analyses to identify immunodominant epitopes for T- and B-cell activation. To enhance immune stimulation and facilitate targeted delivery of the vaccine to specific cells, the selected epitopes were linked to novel carriers, including the extracellular domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a 12-mer Clec9a binding peptide (CBP-12), and a Toll-like receptor 2 (TLR2) peptide ligand. The designed vaccine construct exhibited strong antigenicity along with nonallergenic and nontoxic properties, with favorable physicochemical characteristics. The validated vaccine's tertiary structure underwent evaluation for interactions with CD80/86, Clec9a, and TLR2 through molecular docking and molecular dynamics simulation. The results ensured the vaccine's stability and high affinity for the aforementioned receptors. In silico immune simulations studies revealed robust innate and adaptive immune responses, including enhanced mucosal immunity essential for protection against MPXV. Ultimately, the DNA sequence of the vaccine construct was synthesized and successfully cloned into the pET-22b(+) vector. Our study, through integration of computational predictions, suggests the proposed vaccine's potential efficacy in safeguarding against MPXV; however, further invitro and invivo validations are imperative to assess real-world effectiveness and safety.

A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates

The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates. Immunization with two doses of AR-MPXV5 to cynomolgus macaques effectively elicits antibody responses and cellular responses. Importantly, based on the challenge model with a contemporary MPXV clade II strain, AR-MPXV5 demonstrates effective efficacy in preventing skin lesions, eliminating viremia and reducing viral loads in multiple tissues after challenge in naive male animals. More importantly, AR-MPXV5 is well-tolerated in stable chronic SIV-infected rhesus monkeys, while eliciting comparable MPXV-specific humoral and cellular responses in both naive and SIV-infected monkeys. Together, these results support further clinical development of the AR-MPXV5 vaccine.