Displaying publications 1 - 20 of 44 in total

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  1. Fulltext Cerebral venous sinus thrombosis 2 weeks after the first dose of mRNA SARS-CoV-2 vaccine
    Zakaria Z, Sapiai NA, Ghani ARI
    Acta Neurochir (Wien), 2021 08;163(8):2359-2362.
    PMID: 34101024 DOI: 10.1007/s00701-021-04860-w
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) is a highly transmissible virus and has become pandemic. Part of the prevention of disease spread by the Malaysian government is by getting COVID-19 vaccine. Using the mRNA technology, the Pfizer/BioNTech vaccine is one of the vaccines been approved by the Drug Control Authority in Malaysia. Herein, we report an immediate complication of cerebral VST after the first dose of the Pfizer/BioNTech vaccine.
    Matched MeSH terms: Vaccines, Synthetic/adverse effects*
  2. A probable case of vaccine-induced immune thrombotic thrombocytopenia secondary to Pfizer Comirnaty COVID-19 vaccine
    Goh Cy C, Teng Keat C, Su Kien C, Ai Sim G
    J R Coll Physicians Edinb, 2022 Jun;52(2):113-116.
    PMID: 36146992 DOI: 10.1177/14782715221103660
    The accelerated development of various vaccines against COVID-19 was a global effort to curb the COVID-19 pandemic. As a result, several unique vaccine-related adverse events were observed. Vaccine-induced immune thrombotic thrombocytopenia (VITT) has been recognised as a clinically distinct entity with a predisposition for thrombosis at unusual sites with laboratory features of consumptive coagulopathy in addition to anti-PF4 assay seropositivity. The majority of cases reported were associated with adenoviral-based vectors such as ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Janssen Ad26.COV2.S (Johnson & Johnson). In our online search, we have not found any reports to date of VITT associated with Pfizer-BioNTech Comirnaty mRNA vaccine. We report a case of a previously healthy 76-year-old man who received his first-dose Pfizer Comirnaty vaccine on 11 October 2021 who developed left upper limb swelling on day 2 post-vaccination, which progressively worsened on day 4 post-vaccination. He was confirmed to have left axillary vein thrombosis on computer tomography arteriography/computed tomography venography of left upper limb on day 5 post-vaccination with new onset aphasia with unilateral limb weakness on day 8 post-vaccination. Magnetic resonance imaging/magnetic resonance angiography of the brain confirmed acute left middle cerebral artery thrombosis with infarction. Blood investigations showed thrombocytopenia, elevated D-dimer, hypofibrinogenemia in addition to his unusual sites of thrombosis involving both arterial and venous circulation. His IgG ELISA assay for anti-PF4 antibody was positive.
    Matched MeSH terms: Vaccines, Synthetic
  3. Fulltext Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment
    Monath TP, Seligman SJ, Robertson JS, Guy B, Hayes EB, Condit RC, et al.
    Vaccine, 2015 Jan 01;33(1):62-72.
    PMID: 25446819 DOI: 10.1016/j.vaccine.2014.10.004
    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.
    Matched MeSH terms: Vaccines, Synthetic/adverse effects; Vaccines, Synthetic/genetics
  4. Fulltext Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters
    Ch'ng WC, Stanbridge EJ, Wong KT, Ong KC, Yusoff K, Shafee N
    Virol J, 2012;9:155.
    PMID: 22877087 DOI: 10.1186/1743-422X-9-155
    Enterovirus 71 (EV71) causes severe neurological diseases resulting in high mortality in young children worldwide. Development of an effective vaccine against EV71 infection is hampered by the lack of appropriate animal models for efficacy testing of candidate vaccines. Previously, we have successfully tested the immunogenicity and protectiveness of a candidate EV71 vaccine, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP11-100) protein, in a mouse model of EV71 infection. A drawback of this system is its limited window of EV71 susceptibility period, 2 weeks after birth, leading to restricted options in the evaluation of optimal dosing regimens. To address this issue, we have assessed the NPt-VP11-100 candidate vaccine in a hamster system, which offers a 4-week susceptibility period to EV71 infection. Results obtained showed that the NPt-VP11-100 candidate vaccine stimulated excellent humoral immune response in the hamsters. Despite the high level of antibody production, they failed to neutralize EV71 viruses or protect vaccinated hamsters in viral challenge studies. Nevertheless, these findings have contributed towards a better understanding of the NPt-VP11-100 recombinant protein as a candidate vaccine in an alternative animal model system.
    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/immunology
  5. 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: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology
  6. 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: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics*; Vaccines, Synthetic/immunology*
  7. Approaches towards the development of a vaccine against tuberculosis: recombinant BCG and DNA vaccine
    Mohd Nor N, Musa M
    Tuberculosis (Edinb), 2004;84(1-2):102-9.
    PMID: 14670351 DOI: 10.1016/j.tube.2003.08.011
    The last few years have witnessed intense research on vaccine development against tuberculosis. This has been driven by the upsurge of tuberculosis cases globally, especially those caused by multi-drug-resistant Mycobacterium tuberculosis strains. Various vaccine strategies are currently being developed which can be broadly divided into the so-called living and non-living vaccines. Examples are attenuated members of the M. tuberculosis complex, recombinant mycobacteria, subunit proteins and DNA vaccines. Given current developments, we anticipate that recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M. tuberculosis may need to be cloned in a vaccine construct for the desired efficacy to be achieved. The technique of assembly polymerase chain reaction could facilitate such a cloning procedure.
    Matched MeSH terms: Vaccines, Synthetic
  8. Fulltext A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters
    van Doremalen N, Lambe T, Sebastian S, Bushmaker T, Fischer R, Feldmann F, et al.
    PLoS Negl Trop Dis, 2019 Jun;13(6):e0007462.
    PMID: 31170144 DOI: 10.1371/journal.pntd.0007462
    Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development.
    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology
  9. Cell surface display system for Lactococcus lactis: a novel development for oral vaccine
    Raha AR, Varma NR, Yusoff K, Ross E, Foo HL
    Appl Microbiol Biotechnol, 2005 Jul;68(1):75-81.
    PMID: 15635459
    The food-grade Lactococcus lactis is a potential vector to be used as a live vehicle for the delivery of heterologous proteins for vaccine and pharmaceutical purposes. We constructed a plasmid vector pSVac that harbors a 255-bp single-repeat sequence of the cell wall-binding protein region of the AcmA protein. The recombinant plasmid was transformed into Escherichia coli and expression of the gene fragment was driven by the T7 promoter of the plasmid. SDS-PAGE showed the presence of the putative AcmA' fragment and this was confirmed by Western blot analysis. The protein was isolated and purified using a His-tag affinity column. When mixed with a culture of L. lactis MG1363, ELISA and immunofluorescence assays showed that the cell wall-binding fragment was anchored onto the outer surface of the bacteria. This indicated that the AcmA' repeat unit retained the active site for binding onto the cell wall surface of the L. lactis cells. Stability assays showed that the fusion proteins (AcmA/A1, AcmA/A3) were stably docked onto the surface for at least 5 days. The AcmA' fragment was also shown to be able to strongly bind onto the cell surface of naturally occurring lactococcal strains and Lactobacillus and, with less strength, the cell surface of Bacillus sphericus. The new system designed for cell surface display of recombinant proteins on L. lactis was evaluated for the expression and display of A1 and A3 regions of the VP1 protein of enterovirus 71 (EV71). The A1 and A3 regions of the VP1 protein of EV71 were cloned upstream to the cell wall-binding domains of AcmA protein and successfully expressed as AcmA/A1 and AcmA/A3. Whole-cell ELISA showed the successful display of VP1 protein epitopes of EV71 on the surface of L. lactis. The success of the anchoring system developed in this study for docking the A1 and A3 epitopes of VP1 onto the surface of L. lactis cells opens up the possibilities of peptide and protein display for not only Lactococcus but also for other gram-positive bacteria. This novel way of displaying epitopes on the cell surface of L. lactis and other related organisms should be very useful in the delivery of vaccines and other useful proteins.
    Matched MeSH terms: Vaccines, Synthetic*
  10. Fulltext Evaluation of the immunogenicity of an mRNA vectored Nipah virus vaccine candidate in pigs
    Pedrera M, McLean RK, Medfai L, Thakur N, Todd S, Marsh G, et al.
    Front Immunol, 2024;15:1384417.
    PMID: 38726013 DOI: 10.3389/fimmu.2024.1384417
    Nipah virus (NiV) poses a significant threat to human and livestock populations across South and Southeast Asia. Vaccines are required to reduce the risk and impact of spillover infection events. Pigs can act as an intermediate amplifying host for NiV and, separately, provide a preclinical model for evaluating human vaccine candidate immunogenicity. The aim of this study was therefore to evaluate the immunogenicity of an mRNA vectored NiV vaccine candidate in pigs. Pigs were immunized twice with 100 μg nucleoside-modified mRNA vaccine encoding soluble G glycoprotein from the Malaysia strain of NiV, formulated in lipid nanoparticles. Potent antigen-binding and virus neutralizing antibodies were detected in serum following the booster immunization. Antibody responses effectively neutralized both the Malaysia and Bangladesh strains of NiV but showed limited neutralization of the related (about 80% amino acid sequence identity for G) Hendra virus. Antibodies were also capable of neutralizing NiV glycoprotein mediated cell-cell fusion. NiV G-specific T cell cytokine responses were also measurable following the booster immunization with evidence for induction of both CD4 and CD8 T cell responses. These data support the further evaluation of mRNA vectored NiV G as a vaccine for both pigs and humans.
    Matched MeSH terms: Vaccines, Synthetic/immunology
  11. Self-adjuvanting vaccine against group A streptococcus: application of fibrillized peptide and immunostimulatory lipid as adjuvant
    Azmi F, Ahmad Fuaad AA, Giddam AK, Batzloff MR, Good MF, Skwarczynski M, et al.
    Bioorg Med Chem, 2014 Nov 15;22(22):6401-8.
    PMID: 25438764 DOI: 10.1016/j.bmc.2014.09.042
    Peptides are of great interest to be used as vaccine antigens due to their safety, ease of manufacturing and specificity in generating immune response. There have been massive discoveries of peptide antigens over the past decade. However, peptides alone are poorly immunogenic, which demand co-administration with strong adjuvant to enhance their immunogenicity. Recently, fibril-forming peptides such as Q11 and lipoamino acid-based carrier have been identified to induce substantial immune responses when covalently linked to peptide epitope. In this study, we have incorporated either Q11 or lipoamino acids to a peptide epitope (J14) derived from M protein of group A streptococcus to develop self-adjuvanting vaccines. J14, Q11 and lipoamino acids were also conjugated together in a single vaccine construct in an attempt to evaluate the synergy effect of combining multiple adjuvants. Physicochemical characterization demonstrated that the vaccine constructs folded differently and self-assembled into nanoparticles. Significantly, only vaccine constructs containing double copies of lipoamino acids (regardless in conjugation with Q11 or not) were capable to induce significant dendritic cells uptake and subsequent J14-specific antibody responses in non-sizes dependent manners. Q11 had minimal impact in enhancing the immunogenicity of J14 even when it was used in combination with lipoamino acids. These findings highlight the impact of lipoamino acids moiety as a promising immunostimulant carrier and its number of attachment to peptide epitope was found to have a profound effect on the vaccine immunogenicity.
    Matched MeSH terms: Vaccines, Synthetic/immunology; Vaccines, Synthetic/chemistry*
  12. Fulltext Live recombinant Lactococcus lactis vaccine expressing aerolysin genes D1 and D4 for protection against Aeromonas hydrophila in tilapia (Oreochromis niloticus)
    Anuradha K, Foo HL, Mariana NS, Loh TC, Yusoff K, Hassan MD, et al.
    J Appl Microbiol, 2010 Nov;109(5):1632-42.
    PMID: 20602654 DOI: 10.1111/j.1365-2672.2010.04789.x
    To evaluate a live recombinant Lactococcus lactis vaccine expressing aerolysin genes D1 (Lac-D1ae) and/or D4 (Lac-D4ae) in protection against Aeromonas hydrophila in tilapia (Oreochromis niloticus).
    Matched MeSH terms: Vaccines, Synthetic/genetics*; Vaccines, Synthetic/immunology*
  13. Fulltext Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine
    Ramanathan B, Poh CL, Kirk K, McBride WJ, Aaskov J, Grollo L
    PLoS One, 2016;11(5):e0155900.
    PMID: 27223692 DOI: 10.1371/journal.pone.0155900
    Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.
    Matched MeSH terms: Vaccines, Synthetic/immunology; Vaccines, Synthetic/chemistry
  14. Efficacy of Various HVT Vaccines (Conventional and Recombinant) Against Marek's Disease in Broiler Chickens: Effect of Dose and Age of Vaccination
    Gimeno IM, Cortes AL, Faiz N, Villalobos T, Badillo H, Barbosa T
    Avian Dis, 2016 09;60(3):662-8.
    PMID: 27610727 DOI: 10.1637/11415-040116-Reg.1
    Herpesvirus of turkeys (HVT) has been successfully used as a Marek's disease (MD) vaccine for more than 40 yr. Either alone (broiler chickens) or in combination with vaccines of other serotypes (broilers, broiler breeders, and layers), HVT is used worldwide. In recent years, several vector vaccines based on HVT (rHVT) have been developed. At present, there are both conventional HVT and rHVTs in the market, and it is unknown if all of them confer the same level of protection against MD. The objective of this study was to further characterize the protection conferred by two conventional HVTs (HVT-A and HVT-B) and three recombinant HVTs (rHVT-B, rHVT-C, and rHVT-D) against MD in broiler chickens. In a first study we evaluated the efficacy of two conventional HVTs (HVT-A and HVT-B) administered at different doses (475, 1500, and 4000 PFU) at day of age on the ability to protect against an early challenge with very virulent plus strain 645. In a second experiment we evaluated the protection ability of several HVTs (both conventional and recombinant) when administered in ovo at a dose of 1500 PFU using the same challenge model. Our results show that each HVT product is unique, regardless of being conventional or recombinant, in their ability to protect against MD and might require different PFUs to achieve its maximum efficacy. In Experiment 1, HVT-A at 4000 PFU conferred higher protection (protection index [PI] = 63) than any of the other vaccine protocols (PI ranging from 36 to 47). In Experiment 2, significant differences were found among vaccine protocols with PI varying from 66 (HVT-A) to 15 (rHVT-D). Our results show that each HVT is unique and age at vaccination and vaccine dose greatly affected vaccine efficacy. Furthermore, they highlight the need of following manufacturer's recommendations.
    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/pharmacology
  15. Fulltext The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum
    Abbas MA, Suppian R
    J Infect Dev Ctries, 2019 11 30;13(11):1057-1061.
    PMID: 32087079 DOI: 10.3855/jidc.11331
    INTRODUCTION: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4).

    METHODOLOGY: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively.

    RESULTS: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242.

    CONCLUSIONS: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

    Matched MeSH terms: Vaccines, Synthetic/immunology*; Vaccines, Synthetic/pharmacology
  16. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok® trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age
    Baxter R, Patriarca PA, Ensor K, Izikson R, Goldenthal KL, Cox MM
    Vaccine, 2011 Mar 9;29(12):2272-8.
    PMID: 21277410 DOI: 10.1016/j.vaccine.2011.01.039
    Alternative methods for influenza vaccine production are needed to ensure adequate supplies.
    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/adverse effects; Vaccines, Synthetic/immunology
  17. Development of two salmonella-based oral vaccines against human respiratory syncytial virus
    Azizi Jalilian F, Yusoff K, Suhaimi S, Amini R, Sekawi Z, Jahanshiri F
    J Biol Regul Homeost Agents, 2015 Jan-Mar;29(1):7-18.
    PMID: 25864737
    Human respiratory syncytial virus is the most common cause of bronchiolitis and other respiratory infections in infants and the elderly worldwide. We have developed two new oral vaccines using Salmonella typhi TY21a to carry and express the immunogenic epitopes of RSV fusion (F) and attachment (G) glycoproteins on its surface, separately. To evaluate the efficacy of the designed vaccines, BALB/c mice were orally immunized and then infected with RSV. Immune response analyses showed that cellmediated, mucosal and humoral immunity in the vaccinated mice were significantly enhanced compared to the control group. Both vaccines generated a balanced Th1/Th2 immune response which is crucial for efficiency of vaccines against RSV. Furthermore, histopathological examination proved that these vaccines were safe as they did not cause any Th2-associated adverse effects in the lungs of RSV-infected mice. The findings of this research suggest that Salmonella-F and Salmonella-G vaccine candidates may have strong potential to prevent RSV infection.
    Matched MeSH terms: Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology; Vaccines, Synthetic/pharmacology*
  18. Immune responses in mice and pigs after oral vaccination with rabies virus vectored Nipah disease vaccines
    Shuai L, Ge J, Wen Z, Wang J, Wang X, Bu Z
    Vet Microbiol, 2020 Feb;241:108549.
    PMID: 31928698 DOI: 10.1016/j.vetmic.2019.108549
    Nipah virus (NiV) is a re-emerging zoonotic pathogen that causes high mortality in humans and pigs. Oral immunization in free-roaming animals is one of the most practical approaches to prevent NiV pandemics. We previously generated a recombinant rabies viruses (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, rERAG333E, which contains a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) and serves as an oral vaccine for dog rabies. In this study, we generated two recombinant RABVs, rERAG333E/NiVG and rERAG333E/NiVF, expressing the NiV Malaysian strain attachment glycoprotein (NiV-G) or fusion glycoprotein (NiV-F) gene based on the rERAG333E vector platform. Both rERAG333E/NiVG and rERAG333E/NiVF displayed growth properties similar to those of rERAG333E and caused marked syncytia formation after co-infection in BSR cell culture. Adult and suckling mice intracerebrally inoculated with the recombinant RABVs showed NiV-G and NiV-F expression did not increase the virulence of rERAG333E. Oral vaccination with rERAG333E/NiVG either singularly or combined with rERAG333E/NiVF induced significant NiV neutralizing antibody against NiV and RABV, and IgG to NiV-G or NiV-F in mice and pigs. rERAG333E/NiVG and rERAG333E/NiVF thus appeared to be suitable candidates for further oral vaccines for potential animal targets in endemic areas of NiV disease and rabies.
    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/immunology; Vaccines, Synthetic/standards
  19. Purification and immunogenicity of hemagglutinin from highly pathogenic avian influenza virus H5N1 expressed in Nicotiana benthamiana
    Pua TL, Chan XY, Loh HS, Omar AR, Yusibov V, Musiychuk K, et al.
    Hum Vaccin Immunother, 2017 Feb;13(2):306-313.
    PMID: 27929750 DOI: 10.1080/21645515.2017.1264783
    Highly pathogenic avian influenza (HPAI) H5N1 is an ongoing global health concern due to its severe sporadic outbreaks in Asia, Africa and Europe, which poses a potential pandemic threat. The development of safe and cost-effective vaccine candidates for HPAI is considered the best strategy for managing the disease and addressing the pandemic preparedness. The most potential vaccine candidate is the antigenic determinant of influenza A virus, hemagglutinin (HA). The present research was aimed at developing optimized expression in Nicotiana benthamiana and protein purification process for HA from the Malaysian isolate of H5N1 as a vaccine antigen for HPAI H5N1. Expression of HA from the Malaysian isolate of HPAI in N. benthamiana was confirmed, and more soluble protein was expressed as truncated HA, the HA1 domain over the entire ectodomain of HA. Two different purification processes were evaluated for efficiency in terms of purity and yield. Due to the reduced yield, protein degradation and length of the 3-column purification process, the 2-column method was chosen for target purification. Purified HA1 was found immunogenic in mice inducing H5 HA-specific IgG and a hemagglutination inhibition antibody. This paper offers an alternative production system of a vaccine candidate against a locally circulating HPAI, which has a regional significance.
    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology
  20. Fulltext Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease
    Mire CE, Versteeg KM, Cross RW, Agans KN, Fenton KA, Whitt MA, et al.
    Virol J, 2013 Dec 13;10:353.
    PMID: 24330654 DOI: 10.1186/1743-422X-10-353
    BACKGROUND: Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats. Outbreaks have occurred in Malaysia, Singapore, India, and Bangladesh and have been associated with 40 to 75% case fatality rates. There are currently no vaccines or postexposure treatments licensed for combating human NiV infection.

    METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1.

    CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.

    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology
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