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Does the Development of Vaccines Advance Solutions for Tuberculosis?

AlMatar M, Makky EA, AlMandeal H, Eker E, Kayar B, Var I, et al.

Curr Mol Pharmacol, 2019;12(2):83-104.
PMID: 30474542 DOI: 10.2174/1874467212666181126151948

BACKGROUND: Mycobacterium tuberculosis (Mtb) is considered as one of the most efficacious human pathogens. The global mortality rate of TB stands at approximately 2 million, while about 8 to 10 million active new cases are documented yearly. It is, therefore, a priority to develop vaccines that will prevent active TB. The vaccines currently used for the management of TB can only proffer a certain level of protection against meningitis, TB, and other forms of disseminated TB in children; however, their effectiveness against pulmonary TB varies and cannot provide life-long protective immunity. Based on these reasons, more efforts are channeled towards the development of new TB vaccines. During the development of TB vaccines, a major challenge has always been the lack of diversity in both the antigens contained in TB vaccines and the immune responses of the TB sufferers. Current efforts are channeled on widening both the range of antigens selection and the range of immune response elicited by the vaccines. The past two decades witnessed a significant progress in the development of TB vaccines; some of the discovered TB vaccines have recently even completed the third phase (phase III) of a clinical trial.
OBJECTIVE: The objectives of this article are to discuss the recent progress in the development of new vaccines against TB; to provide an insight on the mechanism of vaccine-mediated specific immune response stimulation, and to debate on the interaction between vaccines and global interventions to end TB.

Matched MeSH terms: Bacterial Vaccines/immunology*
Recombinant vaccines

Barnard RT

Expert Rev Vaccines, 2010 May;9(5):461-3.
PMID: 20450319 DOI: 10.1586/erv.10.48

The Recombinant Vaccines: Strategies for Candidate Discovery and Vaccine Delivery conference, organized by EuroSciCon, hosted a group of UK-based and international scientists from as far afield as Malaysia and Australia. Genomic analyses of pathogens and elucidation of mechanisms of pathogenesis has advanced candidate discovery and development of vaccines. Therefore, it was timely that this conference featured, in addition to detailed expositions of target selection and clinical trials, presentations on manufacturability, scale-up and delivery of vaccines. Ten talks were presented. This meeting report describes the key topics presented and the themes that emerged from this conference.

Matched MeSH terms: Bacterial Vaccines/administration & dosage; Bacterial Vaccines/genetics*; Bacterial Vaccines/immunology*
Characterization of immune response and duration of protection in buffaloes immunized with haemorrhagic septicaemia vaccines

Chandrasekaran S, Kennett L, Yeap PC, Muniandy N, Rani B, Mukkur TK

Vet Microbiol, 1994 Aug 01;41(3):213-9.
PMID: 7975147

Two of the three buffaloes immunized with a non-adjuvanted broth bacterin were found to be protected against experimental challenge at 6 weeks but not at 3 months post-challenge. Similarly all buffaloes (4/4) immunized with alum-precipitated vaccine were protected at 6 months but only 1 of the 2 vaccinated animals were protected at 12 months post-immunization. On the other hand, buffaloes immunized with an oil adjuvant and a double emulsion vaccine were completely protected at 12 months post-immunization. Statistically significant differences between immunized versus non-immune animals became evident at 3 months post-immunization, although analysis of cumulative antibody titres of pre-challenge sera of vaccinated buffaloes surviving versus those succumbing to experimental challenge revealed significant by higher antibody titres in the former as compared to the latter group. These results suggested that there was a relationship between ELISA antibody titres and active protection in buffaloes. There also appeared to be a relationship between cutaneous delayed-type hypersensitivity and active protection in buffaloes. Preliminary analysis of the antibody isotype distribution in the pre-challenge sera of 2 buffaloes vaccinated with the oil adjuvant vaccine revealed predominance of IgG1 and IgG2 subclasses whose role in protection against haemorrhagic septicaemia was not eludicated.

Matched MeSH terms: Bacterial Vaccines/administration & dosage*
Evaluation of combined Pasteurella vaccines in control of sheep pneumonia

Chandrasekaran S, Hizat K, Saad Z, Johara MY, Yeap PC

Br. Vet. J., 1991 Sep-Oct;147(5):437-43.
PMID: 1959015

The effectiveness of an oil adjuvant vaccine (OAV) incorporating locally isolated strains of Pasteurella haemolytica type 7 and Pasteurella multocida types A and D was compared with that of Carovax (Wellcome Laboratories) in imported cross-bred lambs. The criterion of efficacy was the ability of the vaccines to reduce the extent of pneumonic lesions in vaccinated as against unvaccinated control lambs. The OAV produced at this Institute significantly reduced the lung lesions at P less than 0.05 level compared with its control group when challenged with P. haemolytica alone. However, the vaccine was unsatisfactory against P. multocida or combined P. multocida P. haemolytica challenge. Carovax did not produce any significant reduction in the lung lesions caused by P. haemolytica and/or P. multocida.

Matched MeSH terms: Bacterial Vaccines*
Fulltext Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice

Chin CY, Tan SC, Nathan S

Front Cell Infect Microbiol, 2012;2:85.
PMID: 22919676 DOI: 10.3389/fcimb.2012.00085

Burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. As therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outcome. In an earlier study, we reported on the B. pseudomallei serine MprA protease, which is relatively stable over a wide pH and temperature range and digests physiological proteins. The present study was carried out to evaluate the immunogenicity and protective efficacy of the MprA as a potential vaccine candidate. In BALB/c mice immunized with recombinant MprA protease (smBpF4), a significantly high IgG titer was detectable. Isotyping studies revealed that the smBpF4-specific antibodies produced were predominantly IgG(1), proposing that immunization with smBpF4 triggered a Th2 immune response. Mice were immunized with smBpF4 and subsequently challenged with B. pseudomallei via the intraperitoneal route. Whilst control mice succumbed to the infection by day 9, smBpF4-immunized mice were protected against the lethal challenge and survived beyond 25 days post-infection. In conclusion, MprA is immunogenic in melioidosis patients whilst also eliciting a strong immune response upon bacterial challenge in mice and presents itself as a potential vaccine candidate for the treatment of melioidosis.

Matched MeSH terms: Bacterial Vaccines/administration & dosage; Bacterial Vaccines/genetics; Bacterial Vaccines/immunology*
Fulltext Burkholderia vaccines: are we moving forward?

Choh LC, Ong GH, Vellasamy KM, Kalaiselvam K, Kang WT, Al-Maleki AR, et al.

Front Cell Infect Microbiol, 2013;3:5.
PMID: 23386999 DOI: 10.3389/fcimb.2013.00005

The genus Burkholderia consists of diverse species which includes both "friends" and "foes." Some of the "friendly" Burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B. pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, while B. cepacia infection is lethal to cystic fibrosis (CF) patients. Due to the high rate of infectivity and intrinsic resistance to many commonly used antibiotics, together with high mortality rate, B. mallei and B. pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for Burkholderia vaccines. Although the search for a prophylactic therapy candidate continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on development of safe vaccines with high efficacy against B. pseudomallei, B. mallei, and B. cepacia. It can be concluded that further research will enable elucidation of the potential benefits and risks of Burkholderia vaccines.

Matched MeSH terms: Bacterial Vaccines/immunology*
Clinico-pathology and hemato-biochemistry responses in buffaloes infected with Pasteurella multocida type B:2 immunogen outer membrane protein

Chung ELT, Abdullah FFJ, Marza AD, Saleh WMM, Ibrahim HH, Abba Y, et al.

Microb Pathog, 2017 Jan;102:89-101.
PMID: 27894962 DOI: 10.1016/j.micpath.2016.11.015

The aim of this study was to investigate the clinico-pathology and haemato-biochemistry alterations in buffaloes inoculated with Pasteurella multocida type B:2 immunogen outer membrane protein via subcutaneous and oral routes. Nine buffalo heifers were divided equally into 3 treatment groups. Group 1 was inoculated orally with 10 mL of phosphate buffer saline (PBS); Group 2 and 3 were inoculated with 10 mL of outer membrane protein broth subcutaneously and orally respectively. Group 2 buffaloes showed typical haemorrhagic septicaemia clinical signs and were only able to survive for 72 h of the experiment. However, Group 3 buffaloes were able to survive throughout the stipulated time of 21 days of experiment. There were significant differences (p 0.05) in edema between groups except for the lung. This study was a proof that oral route infection of Pasteurella multocida type B:2 immunogen outer membrane protein can be used to stimulate host cell.

Matched MeSH terms: Bacterial Vaccines/immunology
Antigenic potential of a recombinant polyvalent DNA vaccine against pathogenic leptospiral infection

Garba B, Bahaman AR, Zakaria Z, Bejo SK, Mutalib AR, Bande F, et al.

Microb Pathog, 2018 Nov;124:136-144.
PMID: 30138761 DOI: 10.1016/j.micpath.2018.08.028

Leptospirosis is a serious epidemic disease caused by pathogenic Leptospira species. The disease is endemic in most tropical and sub-tropical regions of the world. Currently, there is no effective polyvalent vaccine for prevention against most of the circulating serovars. Moreover, development of an efficient leptospiral vaccine capable of stimulating cross-protective immune responses against a wide range of serovars remains a daunting challenge. This, in part, is associated with the extensive diversity and variation of leptospiral serovars from region to region. In this study, a multi-epitope DNA vaccine encoding highly immunogenic epitopes from LipL32 and LipL41 was designed using in-silico approach. The DNA encoding antigenic epitopes was constructed from conserved pathogenic Leptospira genes (LipL32 and LipL41). Immunization of golden Syrian hamsters with the multi-epitope chimeric DNA vaccine resulted in the production of both agglutinating and neutralizing antibodies as evidence by MAT and in-vitro growth inhibition tests respectively. The antibodies produced reacted against eight different serovars and significantly reduced renal colonization following in vivo challenge. The vaccine was also able to significantly reduce renal colonization which is a very important factor responsible for persistence of leptospires among susceptible and reservoir animal hosts. In conclusion, the leptospiral multi-epitope chimeric DNA vaccine can serve as a potentially effective and safe vaccine against infection with different pathogenic leptospiral serovars.

Matched MeSH terms: Bacterial Vaccines/administration & dosage; Bacterial Vaccines/genetics; Bacterial Vaccines/immunology*
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
Clinical responses in cows vaccinated with a developed prototype killed Staphylococcus aureus mastitis vaccine

Hambali IU, Bhutto KR, Jesse FFA, Lawan A, Odhah MN, Wahid AH, et al.

Microb Pathog, 2018 Nov;124:101-105.
PMID: 30114463 DOI: 10.1016/j.micpath.2018.08.017

Mastitis is an inflammatory condition of the udder that occurs as a result of the release of leucocytes into the udder in a response to bacterial invasion. The major causes of mastitis are an array of gram positive and negative bacteria, however, algae, virus, fungi, mechanical or thermal injury to the gland have also been identified as possible causes. Mastitis vaccines are yet to be developed using Malaysian local isolate of bacteria. The objective of the present experimental trial was to develop a monovalent vaccine against mastitis using S. aureus of Malaysian isolate and to evaluate the clinical responses such as temperature, respiratory rates and heart rates in vaccinated cows. S. aureus is a major causative bacteria in clinical and subclinical types of mastitis in cows. Four concentrations of the bacterin (106, 107, 108 and 109 cfu/ml of the local isolate of S. aureus) were prepared using Aluminium potassium sulfate adjuvant. Thirty cows were grouped into four treatment groups (B, C, D and E) with a fifth group as control (A). These groups were vaccinated intramuscularly(IM) with the prepared monovalent vaccine and its influence on the vital signs were intermittently measured. The mean of rectal temperature was significantly different (p˂ 0.05) at 0hr Post Vaccination [1]" in groups D and E (39.5 ± 0.15 °C and 39.4 ± 0.15 °C respectively) and at 3 h PV in groups C, D and E (39.8 ± 0.14 °C, 39.9 ± 0.14 °C and 40.3 ± 0.14 °C respectively) compared to the control group. This indicated a sharp increased rectal temperatures between 0hr and 3 h PV in groups C, D and E which later declined at 24 h PV. The mean of rectal temperature of group E was significantly different (p˂ 0.05) at weeks 1 and 2 PV (39.87 ± 0.19 °C and 39.80 ± 0.18 °C respectively) compared to the control group. The mean of heart rate was significantly different (p˂ 0.05) at week 1 PV in groups D and E (83.0 ± 3.8 beats/minute and 80.0 ± 3.8 °C respectively) compared to control. A trending decrease was however observed in heart rates of group E from weeks through 4 PV and in group D from weeks 1 through 3 PV. The mean of respiratory rates was significantly different (p˂ 0.05) at week 3 PV in group B and D (31.0 ± 1.2 breaths/minute and 28.0 ± 1.2 breaths/minute) compared to control. In conclusion, this study highlights responses of these vital signs due to vaccination against S. aureus causing mastitis in cows. To the best of our knowledge the findings of this study adds value to the shallow literature on vital signs alterations in cows vaccinated against mastitis as elevated levels of temperature and heart rates of group D and E indicated obvious response.

Matched MeSH terms: Bacterial Vaccines/administration & dosage; Bacterial Vaccines/immunology*
Fulltext Immunogenic Burkholderia pseudomallei outer membrane proteins as potential candidate vaccine targets

Hara Y, Mohamed R, Nathan S

PLoS One, 2009 Aug 05;4(8):e6496.
PMID: 19654871 DOI: 10.1371/journal.pone.0006496

BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. There is no vaccine towards the bacterium available in the market, and the efficacy of many of the bacterium's surface and secreted proteins are currently being evaluated as vaccine candidates.
METHODOLOGY/PRINCIPAL FINDINGS: With the availability of the B. pseudomallei whole genome sequence, we undertook to identify genes encoding the known immunogenic outer membrane protein A (OmpA). Twelve OmpA domains were identified and ORFs containing these domains were fully annotated. Of the 12 ORFs, two of these OmpAs, Omp3 and Omp7, were successfully cloned, expressed as soluble protein and purified. Both proteins were recognised by antibodies in melioidosis patients' sera by Western blot analysis. Purified soluble fractions of Omp3 and Omp7 were assessed for their ability to protect BALB/c mice against B. pseudomallei infection. Mice were immunised with either Omp3 or Omp7, subsequently challenged with 1x10(6) colony forming units (cfu) of B. pseudomallei via the intraperitoneal route, and examined daily for 21 days post-challenge. This pilot study has demonstrated that whilst all control unimmunised mice died by day 9 post-challenge, two mice (out of 4) from both immunised groups survived beyond 21 days post-infection.
CONCLUSIONS/SIGNIFICANCE: We have demonstrated that B. pseudomallei OmpA proteins are immunogenic in mice as well as melioidosis patients and should be further assessed as potential vaccine candidates against B. pseudomallei infection.

Matched MeSH terms: Bacterial Vaccines*
Evaluation of bovine antibody responses to haemorrhagic septicaemia vaccine

Johnson RB, Dawkins HJ, Spencer TL, Saharee AA, Bahaman AR, Ramdani, et al.

Res Vet Sci, 1989 Sep;47(2):277-9.
PMID: 2508206

ELISA and immunoblotting techniques were used to examine the humoral immune response to Pasteurella multocida, in bovine sera from Indonesia and Malaysia. Elevated levels of antibody to a crude lipopolysaccharide preparation were found in vaccinated animals. In addition to the response to lipopolysaccharide, antibodies from the vaccinated cattle strongly labelled five to six of the 40 protein bands in this organism.

Matched MeSH terms: Bacterial Vaccines/immunology*
Serological response of cattle to simultaneous vaccinations against foot-and-mouth disease and haemorrhagic septicaemia

Joseph PG, Hedger RS

Vet Rec, 1984 May 19;114(20):494-6.
PMID: 6330961

In Malaysia, where vaccination campaigns against foot-and-mouth disease and haemorrhagic septicaemia are routinely carried out, it was desirable to determine whether it was safe and efficacious to administer both vaccines simultaneously. A trial group of 104 cattle was divided into three groups; group 1 animals received both vaccines simultaneously, group 2 animals received only foot-and-mouth disease vaccine and group 3 animals received only haemorrhagic septicaemia vaccine. The serological response to vaccinations was monitored at 0, 21 and 35 days by the virus neutralisation test for foot-and-mouth disease and the mouse-protection and indirect haemagglutination tests for haemorrhagic septicaemia. The simultaneous administration of the two inactivated vaccines produced no adverse effects and the serological response did not differ from the response to either vaccine given separately, thus indicating that cattle may be safely and effectively vaccinated simultaneously in this way.

Matched MeSH terms: Bacterial Vaccines/therapeutic use
Intranasal inoculation of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia disease

Kang TL, Chelliah S, Velappan RD, Kabir N, Mohamad J, Nor Rashid N, et al.

Lett Appl Microbiol, 2019 Nov;69(5):366-372.
PMID: 31508837 DOI: 10.1111/lam.13215

We evaluate the efficacy of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia infection through intranasal administration route by targeting the mucosal immunity. The DNA vaccine was constructed and subjected to animal study using the Sprague Dawley (SD) rat. The study was divided into two major parts: (i) active and (ii) passive immunization studies, involving 30 animals for each part. Each group was then divided into five test groups: two test samples G1 and G2 with 50 and 100 µg ml-1 purified DNA vaccine; one positive control G5 with 106 CFU per ml formalin-killed PMB2; and two negative controls, G3 and G4 with normal saline and pVAX1 vector. Both studies were conducted for the determination of immunogenicity by total white blood cell count (TWBC), indirect ELISA and histopathological changes for the presence of the bronchus-associated lymphoid tissue (BALT). Our findings demonstrate that TWBC, IgA and IgG increased after each of the three vaccination regimes: groups G1, G2 and G5. Test samples G1 and G2 showed significant differences (P

Matched MeSH terms: Bacterial Vaccines/administration & dosage*; Bacterial Vaccines/genetics; Bacterial Vaccines/immunology
Designing and evaluation of an antibody-targeted chimeric recombinant vaccine encoding Shigella flexneri outer membrane antigens

Kazi A, Hisyam Ismail CMK, Anthony AA, Chuah C, Leow CH, Lim BH, et al.

Infect Genet Evol, 2020 06;80:104176.
PMID: 31923724 DOI: 10.1016/j.meegid.2020.104176

Shigellosis is one of the most common diseases found in the developing countries, especially those countries that are prone flood. The causative agent for this disease is the Shigella species. This organism is one of the third most common enteropathogens responsible for childhood diarrhea. Since Shigella can survive gastric acidity and is an intracellular pathogen, it becomes difficult to treat. Also, uncontrolled use of antibiotics has led to development of resistant strains which poses a threat to public health. Therefore, there is a need for long term control of Shigella infection which can be achieved by designing a proper and effective vaccine. In this study, emphasis was made on designing a candidate that could elicit both B-cell and T-cell immune response. Hence B- and T-cell epitopes of outer membrane channel protein (OM) and putative lipoprotein (PL) from S. flexneri 2a were computationally predicted using immunoinformatics approach and a chimeric construct (chimeric-OP) containing the immunogenic epitopes selected from OM and PL was designed, cloned and expressed in E. coli system. The immunogenicity of the recombinant chimeric-OP was assessed using Shigella antigen infected rabbit antibody. The result showed that the chimeric-OP was a synthetic peptide candidate suitable for the development of vaccine and immunodiagnostics against Shigella infection.

Matched MeSH terms: Bacterial Vaccines/immunology*
Mucosal and systemic responses of immunogenic vaccines candidates against enteric Escherichia coli infections in ruminants: A review

Lawan A, Jesse FFA, Idris UH, Odhah MN, Arsalan M, Muhammad NA, et al.

Microb Pathog, 2018 Apr;117:175-183.
PMID: 29471137 DOI: 10.1016/j.micpath.2018.02.039

Innumerable Escherichia coli of animal origin are identified, which are of economic significance, likewise, cattle, sheep and goats are the carrier of enterohaemorrhagic E. coli, which are less pathogenic, and can spread to people by way of direct contact and through the contamination of foodstuff or portable drinking water, causing serious illness. The immunization of ruminants has been carried out for ages and is largely acknowledged as the most economical and maintainable process of monitoring E. coli infection in ruminants. Yet, only a limited number of E. coli vaccines are obtainable. Mucosal surfaces are the most important ingress for E. coli and thus mucosal immune responses function as the primary means of fortification. Largely contemporary vaccination processes are done by parenteral administration and merely limited number of E. coli vaccines are inoculated via mucosal itinerary, due to its decreased efficacy. Nevertheless, aiming at maximal mucosal partitions to stimulate defensive immunity at both mucosal compartments and systemic site epitomises a prodigious task. Enormous determinations are involved in order to improve on novel mucosal E. coli vaccines candidate by choosing apposite antigens with potent immunogenicity, manipulating novel mucosal itineraries of inoculation and choosing immune-inducing adjuvants. The target of E. coli mucosal vaccines is to stimulate a comprehensive, effective and defensive immunity by specifically counteracting the antibodies at mucosal linings and by the stimulation of cellular immunity. Furthermore, effective E. coli mucosal vaccine would make vaccination measures stress-free and appropriate for large number of inoculation. On account of contemporary advancement in proteomics, metagenomics, metabolomics and transcriptomics research, a comprehensive appraisal of the immeasurable genes and proteins that were divulged by a bacterium is now in easy reach. Moreover, there exist marvellous prospects in this bourgeoning technologies in comprehending the host bacteria affiliation. Accordingly, the flourishing knowledge could massively guarantee to the progression of immunogenic vaccines against E. coli infections in both humans and animals. This review highlight and expounds on the current prominence of mucosal and systemic immunogenic vaccines for the prevention of E. coli infections in ruminants.

Matched MeSH terms: Bacterial Vaccines/immunology*
Application of Reverse Vaccinology and Immunoinformatic Strategies for the Identification of Vaccine Candidates Against Shigella flexneri

Leow CY, Chuah C, Abdul Majeed AB, Mohd Nor N, Leow CH

Methods Mol Biol, 2022;2414:17-35.
PMID: 34784029 DOI: 10.1007/978-1-0716-1900-1_2

Reverse vaccinology (RV) was first introduced by Rappuoli for the development of an effective vaccine against serogroup B Neisseria meningitidis (MenB). With the advances in next generation sequencing technologies, the amount of genomic data has risen exponentially. Since then, the RV approach has widely been used to discover potential vaccine protein targets by screening whole genome sequences of pathogens using a combination of sophisticated computational algorithms and bioinformatic tools. In contrast to conventional vaccine development strategies, RV offers a novel method to facilitate rapid vaccine design and reduces reliance on the traditional, relatively tedious, and labor-intensive approach based on Pasteur"s principles of isolating, inactivating, and injecting the causative agent of an infectious disease. Advances in biocomputational techniques have remarkably increased the significance for the rapid identification of the proteins that are secreted or expressed on the surface of pathogens. Immunogenic proteins which are able to induce the immune response in the hosts can be predicted based on the immune epitopes present within the protein sequence. To date, RV has successfully been applied to develop vaccines against a variety of infectious pathogens. In this chapter, we apply a pipeline of bioinformatic programs for identification of Shigella flexneri potential vaccine candidates as an illustration immunoinformatic tools available for RV.

Matched MeSH terms: Bacterial Vaccines
Identification of immunogenic proteins from Burkholderia cepacia secretome using proteomic analysis

Mariappan V, Vellasamy KM, Thimma JS, Hashim OH, Vadivelu J

Vaccine, 2010 Feb 3;28(5):1318-24.
PMID: 19944788 DOI: 10.1016/j.vaccine.2009.11.027

Burkholderia cepacia is an opportunistic human pathogen associated with lung infections. Secretory proteins of B. cepacia are known to be involved in virulence and may mediate important host-pathogen interactions. In the present study, secretory proteins isolated from B. cepacia culture supernatant were separated using two-dimensional gel electrophoresis, followed by Western blot analysis to identify the immunogenic proteins. Mice antibodies raised to B. cepacia inactivated whole bacteria, outer membrane protein and culture filtrate antigen detected 74, 104 and 32 immunogenic proteins, respectively. Eighteen of these immunogenic proteins which reacted with all three antibodies were identified and might be potential molecules as a diagnostic marker or a putative candidate vaccine against B. cepacia infections.

Matched MeSH terms: Bacterial Vaccines/immunology
Fulltext Vaccine Efficacy of a Newly Developed Feed-Based Whole-Cell Polyvalent Vaccine against Vibriosis, Streptococcosis and Motile Aeromonad Septicemia in Asian Seabass, Lates calcarifer

Mohamad A, Zamri-Saad M, Amal MNA, Al-Saari N, Monir MS, Chin YK, et al.

Vaccines (Basel), 2021 Apr 10;9(4).
PMID: 33920311 DOI: 10.3390/vaccines9040368

Multiple infections of several bacterial species are often observed under natural farm conditions. The infections would cause a much more significant loss compared to a single infectious agent. Vaccination is an essential strategy to prevent diseases in aquaculture, and oral vaccination has been proposed as a promising technique since it requires no handling of the fish and is easy to perform. This research attempts to develop and evaluate a potential feed-based polyvalent vaccine that can be used to treat multiple infections by Vibrios spp., Streptococcus agalactiae, and Aeromonas hydrophila, simultaneously. The oral polyvalent vaccine was prepared by mixing formalin-killed vaccine of V. harveyi, S. agalactiae, and A. hydrophila strains with commercial feed pellet, and palm oil as an adjuvant was added to improve their antigenicity. Thereafter, a vaccinated feed pellet was tested for feed quality analysis in terms of feed stability in water, proximate nutrient analysis, and palatability, safety, and growth performance using Asian seabass, Lates calcarifer as a fish host model. For immune response analysis, a total of 300 Asian seabass juveniles (15.8 ± 2.6 g) were divided into two groups in triplicate. Fish of group 1 were not vaccinated, while group 2 was vaccinated with the feed-based polyvalent vaccine. Vaccinations were carried out on days 0 and 14 with oral administration of the feed containing the bacterin at 5% body weight. Samples of serum for antibody and lysozyme study and the spleen and gut for gene expression analysis were collected at 7-day intervals for 6 weeks. Its efficacy in protecting fish was evaluated in aquarium challenge. Following vaccination by the polyvalent feed-based vaccine, IgM antibody levels showed a significant (p < 0.05) increase in serum against Vibrio harveyi, Aeromonas hydrophila, and Streptococcus agalactiae and reached the peak at week 3, 5, and 6, respectively. The high-stimulated antibody in the serum remained significantly higher than the control (p < 0.05) at the end of the 6 weeks vaccination trial. Not only that, but the serum lysozyme level was also increased significantly at week 4 (p < 0.05) as compared to the control treatment. The immune-related gene, dendritic cells, C3, Chemokine ligand 4 (CCL4), and major histocompatibility complex class I (MHC I) showed significantly higher expression (p < 0.05) after the fish were vaccinated with the oral vaccine. In the aquarium challenge, the vaccine provided a relative percentage survival of 75 ± 7.1%, 80 ± 0.0%, and 80 ± 0.0% after challenge with V. harveyi, A. hydrophila, and S. agalactiae, respectively. Combining our results demonstrate that the feed-based polyvalent vaccine could elicit significant innate and adaptive immunological responses, and this offers an opportunity for a comprehensive immunization against vibriosis, streptococcosis, and motile aeromonad septicemia in Asian seabass, Lates calcarifer. Nevertheless, this newly developed feed-based polyvalent vaccination can be a promising technique for effective and large-scale fish immunization in the aquaculture industry shortly.

Matched MeSH terms: Bacterial Vaccines
Preliminary study on serum immunoglobulin G responses following intramuscular inoculation of adjuvanted polyhydroxyalkanoate microparticles with Pasteurella multocida vaccine in white rats

Mohamed S, May Amelia TS, Abdullah Amirul AA, Abdul Wahid ME, Bhubalan K

Biologicals, 2021 Jun;71:51-54.
PMID: 33858743 DOI: 10.1016/j.biologicals.2021.03.002

A natural biodegradable polymer, polyhydroxyalkanoate (PHA), was adjuvanted with a vaccine seed to observe the biomaterial's ability in enhancing an immune response in rats. The adjuvant potential of PHA was tested using the whole-killed Pasteurella multocida B:2 (PMB2) vaccine in Sprague Dawley (SD) rats to detect changes in serum immunoglobulin G (IgG) and immunoglobulin M (IgM) responses. A common PHA, poly(3-hydroxybutyrate) [P(3HB)], from Bacillus megaterium UMTKB-1 was constructed into microparticles using the solvent evaporation method. Twelve SD rats were divided into four treatment groups: 1) non-treatment as negative control, 2) P(3HB) adjuvant, 3) PMB2 vaccine, and 4) adjuvanted-P(3HB)/PMB2 vaccine groups, which were intramuscularly vaccinated twice. Immunoglobulins IgG and IgM levels were used as markers of the immune response induced by the adjuvanted-P(3HB)/PMB2 vaccine and analysed over an eight-week study period. The group vaccinated specifically with adjuvanted-P(3HB)/PMB2 vaccine had higher concentrations of immunoglobulins compared to other treatment groups, hence demonstrating the potential of the adjuvant to enhance immune response. Findings showed a need to delay the delivery of the second booster dose to determine the appropriate regime for the adjuvanted-P(3HB)/PMB2 vaccine.

Matched MeSH terms: Bacterial Vaccines/immunology*

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