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Structural vaccinology, molecular simulation and immune simulation approaches to design multi-epitopes vaccine against John Cunningham virus

Suleman M, Khan TA, Ejaz H, Maroof S, Alshammari A, Albekairi NA, et al.

Microb Pathog, 2024 Apr;189:106572.
PMID: 38354987 DOI: 10.1016/j.micpath.2024.106572

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.

Matched MeSH terms: Vaccines*; Vaccines, Subunit/genetics
Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice

Khalid K, Lim HX, Anwar A, Tan SH, Hwang JS, Ong SK, et al.

AAPS PharmSciTech, 2024 Mar 12;25(3):60.
PMID: 38472523 DOI: 10.1208/s12249-024-02778-x

The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins. Nucleotide sequences encoding these peptides representing highly conserved B and T cell epitopes were cloned into a pVAX1 vector to form the pVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine was intranasally or intramuscularly administered to BALB/c mice and evaluations of humoral and cellular immune responses were performed. The intramuscular administration of pVAX1/S2-6EHGFP was associated with a significantly higher percentage of CD8+ T cells expressing IFN-γ when compared with the empty vector and PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFP resulted in robust IgG antibody responses. Sera from mice intramuscularly immunized with pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable of SARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This study demonstrated that the DNA vaccine construct encoding highly conserved immunogenic B and T cell epitopes was capable of eliciting potent humoral and cellular immune responses in mice.

Matched MeSH terms: Vaccines, DNA*
Immunoinformatics-driven In silico vaccine design for Nipah virus (NPV): Integrating machine learning and computational epitope prediction

Shahab M, Iqbal MW, Ahmad A, Alshabrmi FM, Wei DQ, Khan A, et al.

Comput Biol Med, 2024 Mar;170:108056.
PMID: 38301512 DOI: 10.1016/j.compbiomed.2024.108056

The Nipah virus (NPV) is a highly lethal virus, known for its significant fatality rate. The virus initially originated in Malaysia in 1998 and later led to outbreaks in nearby countries such as Bangladesh, Singapore, and India. Currently, there are no specific vaccines available for this virus. The current work employed the reverse vaccinology method to conduct a comprehensive analysis of the entire proteome of the NPV virus. The aim was to identify and choose the most promising antigenic proteins that could serve as potential candidates for vaccine development. We have also designed B and T cell epitopes-based vaccine candidate using immunoinformatics approach. We have identified a total of 5 novel Cytotoxic T Lymphocytes (CTL), 5 Helper T Lymphocytes (HTL), and 6 linear B-cell potential antigenic epitopes which are novel and can be used for further vaccine development against Nipah virus. Then we performed the physicochemical properties, antigenic, immunogenic and allergenicity prediction of the designed vaccine candidate against NPV. Further, Computational analysis indicated that these epitopes possessed highly antigenic properties and were capable of interacting with immune receptors. The designed vaccine were then docked with the human immune receptors, namely TLR-2 and TLR-4 showed robust interaction with the immune receptor. Molecular dynamics simulations demonstrated robust binding and good dynamics. After numerous dosages at varied intervals, computational immune response modeling showed that the immunogenic construct might elicit a significant immune response. In conclusion, the immunogenic construct shows promise in providing protection against NPV, However, further experimental validation is required before moving to clinical trials.

Matched MeSH terms: Vaccines, Subunit/chemistry
Generation of IgG antibodies against Strongyloides stercoralis in mice via immunization with recombinant antigens A133 and Ss-IR

Wong MTJ, Anuar NS, Noordin R, Tye GJ

Acta Trop, 2024 Mar;251:107122.
PMID: 38246399 DOI: 10.1016/j.actatropica.2024.107122

Strongyloidiasis, caused by the nematode Strongyloides stercoralis, remains a threat to global public health, and a vaccine would be useful to control the disease, especially in developing countries. This study aimed to evaluate the efficacy of recombinant proteins, A133 and Ss-IR, as potential vaccine candidates against strongyloidiasis by investigating the humoral and cellular immune responses in immunized mice. Respective antigens were adjuvanted with Complete Freund's Adjuvant (prime) and Incomplete Freund's Adjuvant (boost) and administered intraperitoneally (prime) and subcutaneously (boost) to female BALB/c mice. For antigen-only doses, only antigens were injected without adjuvants. Altogether, 1 prime dose, 4 booster doses, and 2 antigen-only doses were administered successively. ELISAs were conducted to assess the antibody responses, along with flow cytometry and cytokine ELISA to elucidate the cellular immune responses. Results showed that A133 and Ss-IR induced the production of IgG1 and IgG2a, with A133 generating more robust IgG2a responses than Ss-IR. Flow cytometry findings indicated that effector CD8+T-cells and memory B-cells activity were upregulated significantly for A133 only, whereas cytokine ELISA demonstrated that a Th1/Th2/Th17 mixed cell responses were triggered upon vaccination with either antigen. This preliminary study illustrated the good potential of recombinant A133 and Ss-IR as vaccine candidates against S. stercoralis. It provided information on the probable immune mechanism involved in host defence and the elicitation of protection against S. stercoralis.

Matched MeSH terms: Vaccines*
Comparison of adverse effects following immunisation degree after the administration COVID-19 vaccine of different platforms

Bermawi B, Donastin A, Sari NDK, Kurniasari DW, Adriansyah AA, Ferdiansyah MA, et al.

Med J Malaysia, 2024 Mar;79(2):124-127.
PMID: 38553914

INTRODUCTION: Vaccination is an effective way to overcome the spread of Coronavirus Disease 19 (COVID-19). However, it can give rise to adverse event following immunisation (AEFI). AEFI is an important aspect that is assessed in vaccine safety standards. It is assumed that different vaccine platforms can give rise to different degrees of AEFI severity, but so far there have been no studies that discuss the differences in the degree of AEFI on each type of COVID- 19 vaccine platform.
AIM: Evaluate the differences in the degree of AEFI on each type of COVID-19 vaccine platform.
MATERIALS AND METHODS: The research used a quantitative analytical observational design with a cross sectional approach. Data collection from participants was carried out by filling out questionnaires. The collected data was tabulated and statistical analysis was carried out.
RESULTS: A total of 217 respondents who received three doses of vaccine participated in the study. Of the 651 vaccine doses studied, the results showed that there were significant differences in the degree of AEFI between the three types of vaccine platforms. The degree of AEFI was significantly different (p < 0.05) between each type of vaccine platform, with the degree of AEFI starting from the lowest, namely inactivated vaccine, then viral vector vaccine and the highest was nucleic acid vaccine.
CONCLUSION: The degree of AEFI differs significantly between each COVID-19 vaccine platform. The degree of AEFI, from the mildest to the most severe, was inactivated vaccine, viral vector vaccine and nucleic acid vaccine. No serious AEFI was reported.

Matched MeSH terms: Vaccines, Inactivated
Fulltext Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines

Lim CML, Komarasamy TV, Adnan NAAB, Radhakrishnan AK, Balasubramaniam VRMT

Influenza Other Respir Viruses, 2024 Mar;18(3):e13276.
PMID: 38513364 DOI: 10.1111/irv.13276

Every year, influenza virus infections cause significant morbidity and mortality worldwide. They pose a substantial burden of disease, in terms of not only health but also the economy. Owing to the ability of influenza viruses to continuously evolve, annual seasonal influenza vaccines are necessary as a prophylaxis. However, current influenza vaccines against seasonal strains have limited effectiveness and require yearly reformulation due to the virus undergoing antigenic drift or shift. Vaccine mismatches are common, conferring suboptimal protection against seasonal outbreaks, and the threat of the next pandemic continues to loom. Therefore, there is a great need to develop a universal influenza vaccine (UIV) capable of providing broad and durable protection against all influenza virus strains. In the quest to develop a UIV that would obviate the need for annual vaccination and formulation, a multitude of strategies is currently underway. Promising approaches include targeting the highly conserved epitopes of haemagglutinin (HA), neuraminidase (NA), M2 extracellular domain (M2e) and internal proteins of the influenza virus. The identification and characterization of broadly neutralizing antibodies (bnAbs) targeting conserved regions of the viral HA protein, in particular, have provided important insight into novel vaccine designs and platforms. This review discusses universal vaccine approaches presently under development, with an emphasis on those targeting the highly conserved stalk of the HA protein, recent technological advancements used and the future prospects of a UIV in terms of its advantages, developmental obstacles and potential shortcomings.

Matched MeSH terms: Influenza Vaccines*
Advancements in Nipah virus treatment: Analysis of current progress in vaccines, antivirals, and therapeutics

Mishra G, Prajapat V, Nayak D

Immunology, 2024 Feb;171(2):155-169.
PMID: 37712243 DOI: 10.1111/imm.13695

Nipah virus (NiV) causes severe encephalitis in humans. Three NiV strains NiV-Malaysia (NiVM ), NiV Bangladesh (NiVB ), and NiV India (NiVI reported in 2019) have been circulating in South-Asian nations. Sporadic outbreak observed in South-East Asian countries but human to human transmission raises the concern about its pandemic potential. The presence of the viral genome in reservoir bats has further confirmed that NiV has spread to the African and Australian continents. NiV research activities have gained momentum to achieve specific preparedness goals to meet any future emergency-as a result, several potential vaccine candidates have been developed and tested in a variety of animal models. Some of these candidate vaccines have entered further clinical trials. Research activities related to the discovery of therapeutic monoclonal antibodies (mAbs) have resulted in the identification of a handful of candidates capable of neutralizing the virion. However, progress in discovering potential antiviral drugs has been limited. Thus, considering NiV's pandemic potential, it is crucial to fast-track ongoing projects related to vaccine clinical trials, anti-NiV therapeutics. Here, we discuss the current progress in NiV-vaccine research and therapeutic options, including mAbs and antiviral medications.

Matched MeSH terms: Viral Vaccines*
Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013-2015)

Sundaramurthy SSR, Allen KE, Fletcher MA, Liew KF, Borhanuddin B, Ali M, et al.

BMC Infect Dis, 2024 Jan 12;24(1):79.
PMID: 38216882 DOI: 10.1186/s12879-023-08611-3

BACKGROUND: Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015.
METHODS: This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region.
RESULTS: A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged

Matched MeSH terms: Pneumococcal Vaccines
Bibliometric analysis and thematic review of Candida pathogenesis: Fundamental omics to applications as potential antifungal drugs and vaccines

Lim SJ, Muhd Noor ND, Sabri S, Mohamad Ali MS, Salleh AB, Oslan SN

Med Mycol, 2024 Jan 09;62(1).
PMID: 38061839 DOI: 10.1093/mmy/myad126

Invasive candidiasis caused by the pathogenic Candida yeast species has resulted in elevating global mortality. The pathogenicity of Candida spp. is not only originated from its primary invasive yeast-to-hyphal transition; virulence factors (transcription factors, adhesins, invasins, and enzymes), biofilm, antifungal drug resistance, stress tolerance, and metabolic adaptation have also contributed to a greater clinical burden. However, the current research theme in fungal pathogenicity could hardly be delineated with the increasing research output. Therefore, our study analysed the research trends in Candida pathogenesis over the past 37 years via a bibliometric approach against the Scopus and Web of Science databases. Based on the 3993 unique documents retrieved, significant international collaborations among researchers were observed, especially between Germany (Bernhard Hube) and the UK (Julian Naglik), whose focuses are on Candida proteinases, adhesins, and candidalysin. The prominent researchers (Neils Gow, Alistair Brown, and Frank Odds) at the University of Exeter and the University of Aberdeen (second top performing affiliation) UK contribute significantly to the mechanisms of Candida adaptation, tolerance, and stress response. However, the science mapping of co-citation analysis performed herein could not identify a hub representative of subsequent work since the clusters were semi-redundant. The co-word analysis that was otherwise adopted, revealed three research clusters; the cluster-based thematic analyses indicated the severeness of Candida biofilm and antifungal resistance as well as the elevating trend on molecular mechanism elucidation for drug screening and repurposing. Importantly, the in vivo pathogen adaptation and interactions with hosts are crucial for potential vaccine development.

Matched MeSH terms: Vaccines*
Anti-S Antibodies Against SARS-CoV-2 Infection Among Four Types of Vaccines in Malaysia

Lodz NA, Mat Tamizi NF, Abd Mutalip MH, Ganapathy SS, Lin CZ, Ismail R, et al.

Asia Pac J Public Health, 2024 Jan;36(1):96-103.
PMID: 38166431 DOI: 10.1177/10105395231223332

Monitoring SARS-CoV-2 antibody levels can provide insights into a person's immunity to COVID-19 and inform decisions about vaccination and public health measures. Anti-S may be useful as an indicator of an effective immune response. Thus, we conducted this study that aimed to determine the immune response of anti-S antibodies against SARS-CoV-2 for all the vaccine types over time among adult recipients in Malaysia and to determine the associated factors. This study was a cohort that recruited 2513 respondents aged 18 years and above from June to December 2021. Each participant was followed-up for 1-year period from the initial vaccine dose (baseline). We found that the anti-S antibody generally increased for all vaccine types and peaked at two weeks after the second dose vaccination, with Pfizer recipients having the highest median of 100 (100.00-100.00). During the third-month follow-up, the seropositivity of anti-S antibody and the median level decreased for all vaccines. We found that type of vaccines, comorbid status, infection, and booster status were significantly associated with the anti-S antibody level after one year.

Matched MeSH terms: Vaccines*
Fulltext ASVAC2022 : 8th Asian Vaccine Conference

Galagoda GCS, Perera J, de Silva R, Wickramasinghe HT, Dasanayake D, Bravo L, et al.

Hum Vaccin Immunother, 2023 Dec 31;19(1):2165360.
PMID: 36655357 DOI: 10.1080/21645515.2023.2165360

Aiming to further the Immunization Partners in Asia Pacific (IPAP)'s vision of a world where no one suffers from a vaccine preventable disease, the 8th Asian Vaccine Conference (ASVAC 2022) was held in Colombo, Sri Lanka and virtually from 15 to 18, September 2022 (www.asianvaccine.com). This conference followed those held in Siem Reap, Cambodia (2009), Manila, Philippines (2010), Jakarta, Indonesia (2011), Cebu, Philippines (2013), Hanoi, Vietnam (2015), Singapore (2017) and Naypyidaw and Yangon, Myanmar (2019). The ASVAC2022 themed "Immunization: in Era of Pandemics," commenced with the EPI Managers' Workshop, followed by pre-conference workshops and Vaccinology Masterclass, followed by the main conference featuring 5 plenary lectures, 6 partner-led symposia, free paper and poster presentations, and industry-supported lunch and evening sessions. There were over 1830 registered participants, with 112 attending in person and 998 virtually from 63 countries. The conference was organized by IPAP and hosted by the Vaccine and Infectious Disease Forum of Sri Lanka, Sri Lanka College of Pediatricians, Sri Lanka College of Microbiologists and College of General Practitioners of Sri Lanka, with the support of the Ministry of Health, Sri Lanka. The 9th ASVAC is scheduled to be held in Davao City, Philippines in late 2023.

Matched MeSH terms: Vaccines*
Fulltext Effectiveness of vero cell inactivated vaccine against severe acute respiratory infections (SARI) in Sibu, Malaysia: A retrospective test-negative design

Toh TH, Qi YY, Yong SM, Lee JS, Liyana NF, See RY, et al.

Hum Vaccin Immunother, 2023 Dec 31;19(1):2167438.
PMID: 36705277 DOI: 10.1080/21645515.2023.2167438

The effectiveness of the vero cell inactivated vaccine (CoronaVac®) against severe acute respiratory infection (‎SARI)‎ caused by SARS-CoV-2 in the real world was assessed. A matched test-negative case-control design was employed using the web-based national information system, as well as the hospitalization dataset in Sibu Hospital. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, underlying comorbidity, smoking status, and education level. Between 15 March and 30 September 2021, 838 eligible SARI patients were identified from the hospitalization records. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: -28.3 to 74.1) for partial vaccination (after receiving the first dose to 14 days after receiving the second dose), and 76.5% (95% CI: 45.6 to 89.8) for complete vaccination (at 15 days or more after receiving the second dose). This analysis indicated that two doses of CoronaVac® vaccine provided efficacious protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, and performance against new variants need to be studied continuously.

Matched MeSH terms: Vaccines*
Fulltext Hepatitis B and influenza vaccination coverage in healthcare workers, the elderly, and patients with diabetes in Malaysia

Muhammad Azami NA, Abdullah N, Kamalul Ariffin AS, Abdullah MS, Dauni A, Kamaruddin MA, et al.

Hum Vaccin Immunother, 2023 Dec 31;19(1):2170660.
PMID: 36728847 DOI: 10.1080/21645515.2023.2170660

Adult immunization remains to be a neglected issue in developing countries including Malaysia. This nationwide study determined the vaccination coverage of hepatitis B and influenza among Malaysia's healthcare workers (HCWs), the elderly (aged 60 y and above) and patients with diabetes, who are the participants of The Malaysia Cohort Program. The participants were categorized based on their occupation, age and medical history. Self-reported questionnaire was used to assess the participant's hepatitis B and influenza vaccination status. A Chi-square test and logistic regression analyses were performed to determine the risk factors associated with vaccination behavior. The hepatitis B vaccination coverage for healthcare workers, elderly, and patients with diabetes were 34.6%, 10.1% and 9.8%, respectively. The influenza vaccination coverage rates for healthcare workers, the elderly and patients with diabetes were 26.3%, 5.5% and 6.4%, respectively. The Chinese were more likely to be vaccinated against hepatitis B, while Malay was more likely to be vaccinated against influenza. Individuals with higher education and living in urban areas were more likely vaccinated than those with low education levels and who lived in rural areas. The low vaccination coverage for healthcare workers was alarming because hepatitis B and influenza were subsidized for the healthcare workers. The hepatitis B and influenza vaccination coverage among healthcare workers, elderly and patients with diabetes in Malaysia were low. Specific interventions such as educational and awareness programs should be conducted to increase the vaccination rate among adults, especially those at high risk.

Matched MeSH terms: Influenza Vaccines*
Immunoinformatics-based potential multi-peptide vaccine designing against Jamestown Canyon Virus (JCV) capable of eliciting cellular and humoral immune responses

Shahab M, Aiman S, Alshammari A, Alasmari AF, Alharbi M, Khan A, et al.

Int J Biol Macromol, 2023 Dec 31;253(Pt 2):126678.
PMID: 37666399 DOI: 10.1016/j.ijbiomac.2023.126678

Jamestown Canyon virus (JCV) is a deadly viral infection transmitted by various mosquito species. This mosquito-borne virus belongs to Bunyaviridae family, posing a high public health threat in the in tropical regions of the United States causing encephalitis in humans. Common symptoms of JCV include fever, headache, stiff neck, photophobia, nausea, vomiting, and seizures. Despite the availability of resources, there is currently no vaccine or drug available to combat JCV. The purpose of this study was to develop an epitope-based vaccine using immunoinformatics approaches. The vaccine aimed to be secure, efficient, bio-compatible, and capable of stimulating both innate and adaptive immune responses. In this study, the protein sequence of JCV was obtained from the NCBI database. Various bioinformatics methods, including toxicity evaluation, antigenicity testing, conservancy analysis, and allergenicity assessment were utilized to identify the most promising epitopes. Suitable linkers and adjuvant sequences were used in the design of vaccine construct. 50s ribosomal protein sequence was used as an adjuvant at the N-terminus of the construct. A total of 5 CTL, 5 HTL, and 5 linear B cell epitopes were selected based on non-allergenicity, immunological potential, and antigenicity scores to design a highly immunogenic multi-peptide vaccine construct. Strong interactions between the proposed vaccine and human immune receptors, i.e., TLR-2 and TLR-4, were revealed in a docking study using ClusPro software, suggesting their possible relevance in the immunological response to the vaccine. Immunological and physicochemical properties assessment ensured that the proposed vaccine demonstrated high immunogenicity, solubility and thermostability. Molecular dynamics simulations confirmed the strong binding affinities, as well as dynamic and structural stability of the proposed vaccine. Immune simulation suggest that the vaccine has the potential to effectively stimulate cellular and humoral immune responses to combat JCV infection. Experimental and clinical assays are required to validate the results of this study.

Matched MeSH terms: Vaccines, Subunit
Fulltext Vaccines based on the fusion protein consensus sequence protect Syrian hamsters from Nipah virus infection

Lu M, Yao Y, Liu H, Zhang X, Li X, Liu Y, et al.

JCI Insight, 2023 Dec 08;8(23).
PMID: 37917215 DOI: 10.1172/jci.insight.175461

Nipah virus (NiV), a bat-borne paramyxovirus, results in neurological and respiratory diseases with high mortality in humans and animals. Developing vaccines is crucial for fighting these diseases. Previously, only a few studies focused on the fusion (F) protein alone as the immunogen. Numerous NiV strains have been identified, including 2 representative strains from Malaysia (NiV-M) and Bangladesh (NiV-B), which differ significantly from each other. In this study, an F protein sequence with the potential to prevent different NiV strain infections was designed by bioinformatics analysis after an in-depth study of NiV sequences in GenBank. Then, a chimpanzee adenoviral vector vaccine and a DNA vaccine were developed. High levels of immune responses were detected after AdC68-F, pVAX1-F, and a prime-boost strategy (pVAX1-F/AdC68-F) in mice. After high titers of humoral responses were induced, the hamsters were challenged by the lethal NiV-M and NiV-B strains separately. The vaccinated hamsters did not show any clinical signs and survived 21 days after infection with either strain of NiV, and no virus was detected in different tissues. These results indicate that the vaccines provided complete protection against representative strains of NiV infection and have the potential to be developed as a broad-spectrum vaccine for human use.

Matched MeSH terms: Viral Vaccines*
A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia

Goa Y, Du JG, Jirapattharasate C, Galon E, Ji SW, Ran ZG, et al.

Trop Biomed, 2023 Dec 01;40(4):400-405.
PMID: 38308826 DOI: 10.47665/tb.40.4.004

Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPBm4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPBm4 (rSUMO-CPBm4) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPBm4, rSUMO-CPBm4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPBm4 nor rSUMO-CPBm4 was lethal to mice. Although rCPBm4 and rSUMO-CPBm4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPBm4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPBm4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.

Matched MeSH terms: Bacterial Vaccines
The impact of geo-political socio-economic factors on vaccine dissemination trends: a case-study on COVID-19 vaccination strategies

Chauhan R, Varma G, Yafi E, Zuhairi MF

BMC Public Health, 2023 Nov 02;23(1):2142.
PMID: 37919737 DOI: 10.1186/s12889-023-17000-z

BACKGROUND: The world in recent years has seen a pandemic of global scale. To counter the widespread loss of life and severe repercussions, researchers developed vaccinations at a fast pace to immunize the population. While the vaccines were developed and tested through extensive human trials, historically vaccines have been known to evoke mixed sentiments among the generic demographics. In the proposed study, we aim to reveal the impact of political and socio-economic factors on SARS-Cov-2 vaccination trends observed in two hundred and seventeen countries spread across the six continents.
METHODS: The study had hypothesized that the citizens who have lower trust in their government would be less inclined towards vaccination programs. To test this hypothesis, vaccination trends of nations under authoritarian rule were compared against democratic nations. Further, the study was synthesized with Cov-2 vaccination data which was sourced from Our World Data repository, which was sampled among 217 countries spread across the 6 continents. The study was analyzed with exploratory data analysis and proposed with relevance and impacting factor that was considered for vaccine dissemination in comparison with the literacy rate of the nations. Another impacting factor the study focused on for the vaccination dissemination trends was the health expenses of different nations. The study has been synthesized on political and socio-economic factors where the features were ardently study in retrospect of varied socio- economic features which may include country wise literacy rate, overall GDP rate, further we substantiated the work to address the political factors which are discussed as the country status of democratic or having other status.
RESULTS: The comparison of trends showed that dissemination of SARS-Cov-2 vaccines had been comparable between the two-opposing types of governance. The major impact factor behind the wide acceptance of the SARS-Cov-2 vaccine was the expenditure done by a country on healthcare. These nations used a large number of vaccines to administer to their population and the trends showed positive growth. The overall percentage of vaccine utilized by countries in quantitative terms are Pfizer/BioNTech (17.55%), Sputnik V (7.08%), Sinovac (6.98%), Sinopharm/Beijing (10.04%), Oxford/AstraZeneca (19.56%), CanSino (2.85%), Moderna (12.05%), Covaxin (3.28%), JohnsonandJohnson (10.89%), Sputnik Light (3.07%), Novavax (3.49%). While the nations with the lowest healthcare expenses failed to keep up with the demand and depended on vaccines donated by other countries to protect their population.
CONCLUSIONS: The analysis revealed strong indicators that the nations which spend more on healthcare were the ones that had the best SARS-Cov-2 vaccination rollout. To further support decision-making in the future, countries should address the trust and sentiment of their citizens towards vaccination. For this, expenses need to be made to develop and promote vaccines and project them as positive health tools.

Matched MeSH terms: Vaccines*
Fulltext Report on the seventh meeting of national control laboratories for vaccines and biologicals of the WHO Western Pacific and South-East Asia member states

Shim SB, Choi CW, Shin JH, Kim JW, Schepelmann S, Jung JH, et al.

Biologicals, 2023 Nov;84:101712.
PMID: 37797484 DOI: 10.1016/j.biologicals.2023.101712

The Biregional Network of National Control Laboratories (NCLs) of the WHO Western Pacific and South-East Asia Regions has been meeting annually since 2018 to enhance NCLs' voluntary participation capacity. Its seventh meeting was hosted by the Korea National Institute of Food and Drug Safety Evaluation (NIFDS) of the Ministry of Food and Drug Safety (MFDS), in conjunction with the Global Bio Conference, in Seoul on September 6, 2022. Over 60 participants from seven countries, (India, Indonesia, Japan, Korea, Malaysia, the Philippines, and Vietnam) attended the meeting on-site and online. The theme of this meeting was 'Quality Control Issues and International Trends for Biologicals including Vaccines and Plasma-Derived Medicinal Products.' Three special speeches were presented on sharing the quality control system for biologicals, including NCLs' considerations in preparing the WHO Listed Authorities and sharing MFDS experiences. Furthermore, the participating NCLs shared country-specific issues related to national lot releases during the COVID-19 pandemic and acknowledged the meeting's crucial role in response preparedness for pandemic emergencies and enhancing regulatory capacity through coalitions and information exchange among NCLs. The NIFDS will cooperate closely with other Asian NCLs to enhance biological product quality control, aiming to establish regional standards and standardize test methods through collaboration.

Matched MeSH terms: Vaccines*
Fulltext Cost effectiveness of quadrivalent influenza vaccines in the elderly population of Malaysia

Aljunid SM, Mad Tahir NS, Ismail A, Abdul Aziz AF, Azzeri A, Zafirah SA, et al.

Sci Rep, 2023 Oct 31;13(1):18771.
PMID: 37907537 DOI: 10.1038/s41598-023-46079-y

The economic burden of influenza is a significant issue within healthcare system, related to higher medical costs particularly among the elderly. Yet, influenza vaccination rates in the elderly in Malaysia were considerably low as it is not part of Malaysia's national immunization program, with substantial mortality and morbidity consequences. Therefore, we conducted a cost-effectiveness analysis of quadrivalent influenza vaccine (QIV) for the elderly in Malaysia compared with the current no-vaccination policy. A static cost-utility model, with a lifetime horizon based on age, was used for the analysis to assess the cost-effectiveness and health outcomes associated with QIV. Univariate and probabilistic sensitivity analyses were performed to test the effects of variations in the parameters. The use of QIV in Malaysia's elderly population would prevent 66,326 potential influenza cases and 888 potential deaths among the elderly, leading to 10,048 potential quality-adjusted life years (QALYs) gained. The QIV would also save over USD 4.4 million currently spent on influenza-related hospitalizations and reduce productivity losses by approximately USD 21.6 million. The ICER per QALY gained from a third-party payer's perspective would be USD 2216, which is lower than the country's gross domestic product per capita. A QIV-based vaccination program in the elderly was found to be highly cost-effective, therefore would reduce the financial burden of managing influenza and reduce pre-mature death related to this disease.

Matched MeSH terms: Influenza Vaccines*
Fulltext The development of DNA vaccines against SARS-CoV-2

Khalid K, Poh CL

Adv Med Sci, 2023 Sep;68(2):213-226.
PMID: 37364379 DOI: 10.1016/j.advms.2023.05.003

BACKGROUND: The COVID-19 pandemic exerted significant impacts on public health and global economy. Research efforts to develop vaccines at warp speed against SARS-CoV-2 led to novel mRNA, viral vectored, and inactivated vaccines being administered. The current COVID-19 vaccines incorporate the full S protein of the SARS-CoV-2 Wuhan strain but rapidly emerging variants of concern (VOCs) have led to significant reductions in protective efficacies. There is an urgent need to develop next-generation vaccines which could effectively prevent COVID-19.
METHODS: PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2023.
RESULTS: A promising solution to the problem of emerging variants is a DNA vaccine platform since it can be easily modified. Besides expressing whole protein antigens, DNA vaccines can also be constructed to include specific nucleotide genes encoding highly conserved and immunogenic epitopes from the S protein as well as from other structural/non-structural proteins to develop effective vaccines against VOCs. DNA vaccines are associated with low transfection efficiencies which could be enhanced by chemical, genetic, and molecular adjuvants as well as delivery systems.
CONCLUSIONS: The DNA vaccine platform offers a promising solution to the design of effective vaccines. The challenge of limited immunogenicity in humans might be solved through the use of genetic modifications such as the addition of nuclear localization signal (NLS) peptide gene, strong promoters, MARs, introns, TLR agonists, CD40L, and the development of appropriate delivery systems utilizing nanoparticles to increase uptake by APCs in enhancing the induction of potent immune responses.

Matched MeSH terms: Vaccines, DNA*

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