Displaying publications 61 - 80 of 743 in total

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  1. Four is better than nine. a combined diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine for routine immunization in Malaysia
    Wong SL, Soosai P, Teoh YL, Han HH, Lefevre I, Bock HL
    Southeast Asian J. Trop. Med. Public Health, 2008 May;39(3):474-83.
    PMID: 18564687
    Malaysian infants would have to receive nine injections during the first few months of life in order to be protected against disease caused by hepatitis B (HBV), diphtheria, tetanus, pertussis and Haemophilus influenzae type b (Hib) if single HBV and Hib vaccines were used. We evaluated a combined DTPw-HBV/Hib vaccine administered at 1.5, 3 and 5 months after a birth dose of hepatitis B vaccine (HBV). One month after completion of the primary vaccination, 99% of subjects had seroprotective anti-HBV antibody levels, and at least 98% had seroprotective antibodies against diphtheria, tetanus, and Hib, and were seropositive for pertussis antibodies. The immune response to the combined vaccine was comparable to that induced by separate injections with DTPw, HBV and Hib vaccines. Overall, the DTPw-HBV/Hib vaccine was as well tolerated as separate administration of DTPw, HBV and Hib vaccines. The combined DTPw-HBV/Hib vaccine induces protection against five diseases as recommended in the Malaysian routine vaccination schedule. Use of the combined DTPw-HBV/Hib vaccine can reduce the required number of injections from nine to four in the first few months of life.
    Matched MeSH terms: Hepatitis B Vaccines/administration & dosage*; Hepatitis B Vaccines/adverse effects; Hepatitis B Vaccines/immunology; Vaccines, Combined/administration & dosage; Vaccines, Combined/adverse effects; Vaccines, Combined/immunology; Haemophilus Vaccines/administration & dosage*; Haemophilus Vaccines/adverse effects; Haemophilus Vaccines/immunology; Vaccines, Conjugate/adverse effects; Vaccines, Conjugate/immunology
  2. Vaccine-induced immune thrombocytopaenia purpura in autologous haematopoietic stem cell transplantation
    Wan Jamaludin WF, Kok WH, Loong L, Palaniappan SK, Zakaria MZ, Ong TC, et al.
    Med J Malaysia, 2018 12;73(6):430-432.
    PMID: 30647224
    Immune Thrombocytopenia Purpura (ITP) secondary to vaccinations is rare, especially after autologous hematopoietic stem cell transplantation (HSCT). A 31-yearold female received autologous HSCT for relapsed Hodgkin Disease, with platelet engraftment at Day+14. One week after receiving second scheduled vaccinations, she developed severe thrombocytopenia (3x109/L) associated with pharyngeal hematoma. Bone marrow (BM) examinations were consistent with ITP, possibly secondary to Influenza vaccine. Platelet increment was poor despite high dose corticosteroids, intravenous immunoglobulin (IVIG), Danazol and Eltrombopag. A repeated BM biopsy was in agreement with ITP. Re-treatment with tapering doses of prednisolone resulted in stable platelet counts at 120x109/L a year later.
    Matched MeSH terms: Influenza Vaccines/adverse effects; Vaccines/adverse effects*; Hepatitis B Vaccines/adverse effects; Haemophilus Vaccines/adverse effects; Pneumococcal Vaccines/adverse effects
  3. Cloning, expression, and purification of recombinant protein from a single synthetic multivalent construct of Mycobacterium tuberculosis
    Fang CM, Zainuddin ZF, Musa M, Thong KL
    Protein Expr Purif, 2006 Jun;47(2):341-7.
    PMID: 16510294 DOI: 10.1016/j.pep.2005.12.007
    Tuberculosis remains a major infectious disease with over 8 million new cases and 2 million deaths annually. Therefore, a vaccine more potent than BCG is desperately needed. In this regard, an approximately 800 bp DNA encoding a mycobacterial synthetic gene designated as VacIII (containing ubiquitin gene UbGR and four immunogenic mycobacterial epitopes or genes of ESAT-6, Phos1, Hsp 16.3, and Mtb8.4) was sub-cloned into a bacterial expression vector of pRSET-B resulting in a 6 x His-VacIII fusion gene construction. This recombinant clone was over expressed in Escherichia coli BL-21 (DE-3). The expressed fusion protein was found almost entirely in the insoluble form (inclusion bodies) in cell lysate. The inclusion bodies were solubilized with 8M urea and the recombinant protein was purified by Ni-NTA column and dialyzed by urea gradient dialysis. This method produced a relatively high yield of recombinant VacIII protein and the cloned VacIII gene offers the potential development of other vaccine formats such as DNA vaccine and recombinant vaccine.
    Matched MeSH terms: Vaccines, Acellular/biosynthesis; Vaccines, Acellular/genetics; Vaccines, Acellular/immunology; Vaccines, Acellular/isolation & purification; Tuberculosis Vaccines/biosynthesis*; Tuberculosis Vaccines/genetics; Tuberculosis Vaccines/immunology; Tuberculosis Vaccines/isolation & purification
  4. Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children
    Lum LC, Borja-Tabora CF, Breiman RF, Vesikari T, Sablan BP, Chay OM, et al.
    Vaccine, 2010 Feb 10;28(6):1566-74.
    PMID: 20003918 DOI: 10.1016/j.vaccine.2009.11.054
    Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).
    Matched MeSH terms: Influenza Vaccines/administration & dosage; Influenza Vaccines/immunology*; Vaccines, Attenuated/administration & dosage; Vaccines, Attenuated/immunology; Vaccines, Combined/administration & dosage; Vaccines, Combined/immunology
  5. Recent progress in adjuvant discovery for peptide-based subunit vaccines
    Azmi F, Ahmad Fuaad AA, Skwarczynski M, Toth I
    Hum Vaccin Immunother, 2014;10(3):778-96.
    PMID: 24300669
    Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.
    Matched MeSH terms: Vaccines, Subunit/administration & dosage; Vaccines, Subunit/immunology*
  6. 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: Influenza Vaccines/administration & dosage; Influenza Vaccines/adverse effects; Influenza Vaccines/immunology*; Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/adverse effects; Vaccines, Synthetic/immunology; Vaccines, Inactivated/administration & dosage; Vaccines, Inactivated/adverse effects; Vaccines, Inactivated/immunology
  7. Virology--11th international congress. 9-13 August 1999, Sydney, Australia
    Fooks A
    IDrugs, 1999 Nov;2(11):1136-8.
    PMID: 16113984
    The main theme of this conference was understanding the complex biology of viruses in order to design appropriate vaccines for human use. The use of both plant and animal viruses as vectors for delivery vehicles was widely discussed. These engineered viruses could be delivered in oral formulations or, in the case of plant viruses, grown in the plant host and used as edible vaccines. New technologies for producing highly attenuated vaccines through the use of 'molecular clone technologies' were shown to be highly efficacious in animal models. While new vaccine candidates are being generated against many established viral diseases, there remains a threat from HIV, virulent strains of influenza and newly emerging viruses for which no vaccines are currently available. Emerging viruses, such as the Hendra-like virus called Nipah, which emerged in pig herds in Malaysia and Singapore in 1998, has posed a severe economic threat to the region. The subsequent spread of Nipah virus to humans and the threat of epidemic spread was evidence that virologists should not become complacent.
    Matched MeSH terms: Influenza Vaccines; Vaccines, Attenuated; Vaccines, Edible
  8. Fulltext Safety and Efficacy of Pneumococcal Vaccination in Pediatric Nephrotic Syndrome
    Goonewardene ST, Tang C, Tan LT, Chan KG, Lingham P, Lee LH, et al.
    Front Pediatr, 2019;7:339.
    PMID: 31456997 DOI: 10.3389/fped.2019.00339
    Nephrotic syndrome affects both children and adults. Idiopathic nephrotic syndrome is reported to be one of the most frequent renal pathologies in childhood. Nephrotic children are at high risk for severe pneumococcal infections as one of the life-threatening complications of nephrotic syndrome due to involvement of the immunosuppressive regimen and the acquired immune deficiency induced by nephrotic syndrome including decreased plasma IgG and low complement system components. Aiming to prevent pneumococcal infection is of paramount importance especially in this era of ever-increasing pneumococcal resistance to penicillins and cephalosporins. The pneumococcal vaccines currently available are inactivated vaccines-the two main forms in use are polysaccharide vaccines and conjugated vaccines. However, the data supporting the use of these vaccines and to guide the timing and dosage recommendations is still limited for nephrotic children. Thus, this review discusses the evidences of immunogenicity and safety profile of both vaccinations on nephrotic patients as well as the effect of nephrotic syndrome treatment on vaccine seroresponses.
    Matched MeSH terms: Vaccines, Inactivated; Vaccines, Conjugate; Pneumococcal Vaccines
  9. COVID-19 vaccines and herd immunity: Perspectives, challenges and prospects
    Wong RSY
    Malays J Pathol, 2021 Aug;43(2):203-217.
    PMID: 34448786
    The coronavirus disease 2019 (COVID-19) is one of the biggest public health threats in the 21st century. Nearly every country in the world has been affected by COVID-19. The magnitude of the problem, with over 179 million confirmed cases and 3.8 million deaths worldwide, has driven researchers to search for vaccines to combat the disease. The discovery and development of a new vaccine, from the initial stage to the vaccine finally reaching the patients, usually take many years. However, given the urgency of the situation, many clinical trials on the COVID-19 vaccines have been conducted at extraordinary speed, whereas several vaccines against SARS-CoV-2 are being administered worldwide. This article gives an overview of the different types of COVID-19 vaccines, with a focus on those with promising results and are commonly used worldwide. It also gives an overview of herd immunity and discusses the challenges in achieving herd immunity through the global vaccination campaigns. Last but not least, some strategies that may be used to address these challenges are discussed.
    Matched MeSH terms: Vaccines/immunology*; Vaccines/pharmacology
  10. Fulltext Microarray Profiling of Vaccination-Induced Antibody Responses to SARS-CoV-2 Variants of Interest and Concern
    Svetlova J, Gustin D, Manuvera V, Shirokov D, Shokina V, Prusakov K, et al.
    Int J Mol Sci, 2022 Oct 30;23(21).
    PMID: 36362010 DOI: 10.3390/ijms232113220
    Mutations in surface proteins enable emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to escape a substantial fraction of neutralizing antibodies and may thus weaken vaccine-driven immunity. To compare available vaccines and justify revaccination, rapid evaluation of antibody (Ab) responses to currently circulating SARS-CoV-2 variants of interest (VOI) and concern (VOC) is needed. Here, we developed a multiplex protein microarray-based system for rapid profiling of anti-SARS-CoV-2 Ab levels in human sera. The microarray system was validated using sera samples from SARS-CoV-2-free donors and those diagnosed with COVID-19 based on PCR and enzyme immunoassays. Microarray-based profiling of vaccinated donors revealed a substantial difference in anti-VOC Ab levels elicited by the replication-deficient adenovirus vector-base (Sputnik V) and whole-virion (CoviVac Russia COVID-19) vaccines. Whole-virion vaccine-induced Abs showed minor but statistically significant cross-reactivity with the human blood coagulation factor 1 (fibrinogen) and thrombin. However, their effects on blood clotting were negligible, according to thrombin time tests, providing evidence against the concept of pronounced cross-reactivity-related side effects of the vaccine. Importantly, all samples were collected in the pre-Omicron period but showed noticeable responses to the receptor-binding domain (RBD) of the Omicron spike protein. Thus, using the new express Ab-profiling system, we confirmed the inter-variant cross-reactivity of the anti-SARS-CoV-2 Abs and demonstrated the relative potency of the vaccines against new VOCs.
    Matched MeSH terms: Viral Vaccines/genetics; Viral Vaccines/pharmacology
  11. Fulltext Economic impact of switching from partially combined vaccine "Pentaxim® and hepatitis B" to fully combined vaccine "Hexaxim®" in the Malaysian National Immunization Program
    Aljunid SM, Al Bashir L, Ismail AB, Aizuddin AN, Rashid SAZA, Nur AM
    BMC Health Serv Res, 2022 Jan 05;22(1):34.
    PMID: 34986870 DOI: 10.1186/s12913-021-07428-7
    BACKGROUND: The decision to implement new vaccines should be supported by public health and economic evaluations. Therefore, this study was primarily designed to evaluate the economic impact of switching from partially combined vaccine (Pentaxim® plus hepatitis B) to fully combined vaccine (Hexaxim®) in the Malaysian National Immunization Program (NIP) and to investigate healthcare professionals (HCPs)' and parents'/caregivers' perceptions.

    METHODS: In this economic evaluation study, 22 primary healthcare centers were randomly selected in Malaysia between December 2019 and July 2020. The baseline immunization schedule includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses), whereas the alternative scheme includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses) and hepatitis B (one dose) administered at birth. Direct medical costs were extracted using a costing questionnaire and an observational time and motion chart. Direct non-medical (cost for transportation) and indirect costs (loss of productivity) were derived from parents'/caregivers' questionnaire. Also, HCPs' and parent's/caregivers' perceptions were investigated using structured questionnaires.

    RESULTS: The cost per dose of Pentaxim® plus hepatitis B vs. Hexaxim® for the baseline scheme was Malaysian ringgit (RM) 31.90 (7.7 United States dollar [USD]) vs. 17.10 (4.1 USD) for direct medical cost, RM 54.40 (13.1 USD) vs. RM 27.20 (6.6 USD) for direct non-medical cost, RM 221.33 (53.3 USD) vs. RM 110.66 (26.7 USD) for indirect cost, and RM 307.63 (74.2 USD) vs. RM 155.00 (37.4 USD) for societal (total) cost. A similar trend was observed for the alternative scheme. Compared with Pentaxim® plus hepatitis B, total cost savings per dose of Hexaxim® were RM 137.20 (33.1 USD) and RM 104.70 (25.2 USD) in the baseline and alternative scheme, respectively. Eighty-four percent of physicians and 95% of nurses supported the use of Hexaxim® in the NIP. The majority of parents/caregivers had a positive perception regarding Hexaxim® vaccine in various aspects.

    CONCLUSIONS: Incorporation of Hexaxim® within Malaysian NIP is highly recommended because the use of Hexaxim® has demonstrated substantial direct and indirect cost savings for healthcare providers and parents/caregivers with a high percentage of positive perceptions, compared with Pentaxim® plus hepatitis B.

    TRIAL REGISTRATION: Not applicable.

    Matched MeSH terms: Hepatitis B Vaccines; Vaccines, Combined; Haemophilus Vaccines
  12. 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: Influenza Vaccines/administration & dosage; Influenza Vaccines/genetics; Influenza Vaccines/immunology*; Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology; Vaccines, Subunit/administration & dosage; Vaccines, Subunit/genetics; Vaccines, Subunit/immunology
  13. Fulltext Knowledge, attitudes, and practices of the general population of Pakistan regarding typhoid conjugate vaccine: findings of a cross-sectional study
    Tahir MJ, Zaman M, Saffi J, Asghar MS, Tariq W, Ahmed F, et al.
    Front Public Health, 2023;11:1151936.
    PMID: 37333546 DOI: 10.3389/fpubh.2023.1151936
    Typhoid fever, a common enteric disease in Pakistan, caused by Salmonella typhi, is becoming an extended drug-resistant organism and is preventable through the typhoid conjugate vaccine (TCV). Public adherence to preventive measures is influenced by knowledge and attitude toward the vaccine. This study investigates the knowledge, attitudes, and practices of the general population of Pakistan toward TCV. The differences in mean scores and factors associated with typhoid conjugate vaccine knowledge, attitudes, and practices were investigated. A total of 918 responses were received with a mean age of 25.9 ± 9.6, 51% were women, and 59.6% had graduation-level education. The majority of them responded that vaccines prevent illness (85.3%) and decrease mortality and disability (92.6%), and typhoid could be prevented by vaccination (86.7%). In total, 77.7 and 80.8% considered TCV safe and effective, respectively. Of 389 participants with children, 53.47% had vaccinated children, according to the extended program on immunization (EPI). Higher family income has a higher odds ratio (OR) for willingness toward booster dose of TCV [crude odds ratio (COR) = 4.920, p-value <0.01; adjusted odds ratio (aOR) = 2.853, value of p <0.001], and negative attitude regarding the protective effect of TCV has less willingness toward the booster dose with statistical significance (COR = 0.388, value of p = 0.017; aOR = 0.198, value of p = 0.011). The general population of Pakistan had a good level of knowledge about the benefits of TCV, and attitude and practices are in favor of the usage of TCV. However, a few religious misconceptions are prevalent in public requiring the efforts to overcome them to promote the usage of vaccines to prevent the disease and antibiotic resistance.
    Matched MeSH terms: Typhoid-Paratyphoid Vaccines*; Vaccines, Conjugate
  14. Fulltext Induction of humoral and cell-mediated immune responses by hepatitis B virus epitope displayed on the virus-like particles of prawn nodavirus
    Yong CY, Yeap SK, Goh ZH, Ho KL, Omar AR, Tan WS
    Appl Environ Microbiol, 2015 Feb;81(3):882-9.
    PMID: 25416760 DOI: 10.1128/AEM.03695-14
    Hepatitis B virus (HBV) is a deadly pathogen that has killed countless people worldwide. Saccharomyces cerevisiae-derived HBV vaccines based upon hepatitis B surface antigen (HBsAg) is highly effective. However, the emergence of vaccine escape mutants due to mutations on the HBsAg and polymerase genes has produced a continuous need for the development of new HBV vaccines. In this study, the "a" determinant within HBsAg was displayed on the recombinant capsid protein of Macrobrachium rosenbergii nodavirus (MrNV), which can be purified easily in a single step through immobilized metal affinity chromatography (IMAC). The purified protein self-assembled into virus-like particles (VLPs) when observed under a transmission electron microscope (TEM). Immunization of BALB/c mice with this chimeric protein induced specific antibodies against the "a" determinant. In addition, it induced significantly more natural killer and cytotoxic T cells, as well as an increase in interferon gamma (IFN-γ) secretion, which are vital for virus clearance. Collectively, these findings demonstrated that the MrNV capsid protein is a potential carrier for the HBV "a" determinant, which can be further extended to display other foreign epitopes. This paper is the first to report the application of MrNV VLPs as a novel platform to display foreign epitopes.
    Matched MeSH terms: Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology; Hepatitis B Vaccines/administration & dosage; Hepatitis B Vaccines/genetics; Hepatitis B Vaccines/immunology*; Vaccines, Virus-Like Particle/administration & dosage; Vaccines, Virus-Like Particle/genetics; Vaccines, Virus-Like Particle/immunology*
  15. Vaccination in Southeast Asia--reducing meningitis, sepsis and pneumonia with new and existing vaccines
    Richardson A, Morris DE, Clarke SC
    Vaccine, 2014 Jul 16;32(33):4119-23.
    PMID: 24907487 DOI: 10.1016/j.vaccine.2014.05.062
    Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are leading causes of vaccine-preventable diseases such as meningitis, sepsis and pneumonia. Although there has been much progress in the introduction of vaccines against these pathogens, access to vaccines remains elusive in some countries. This review highlights the current S. pneumoniae, H. influenzae type b, and N. meningitidis immunization schedules in the 10 countries belonging to the Association of Southeast Asian Nations (ASEAN). Epidemiologic studies may be useful for informing vaccine policy in these countries, particularly when determining the cost-effectiveness of introducing new vaccines.
    Matched MeSH terms: Haemophilus Vaccines*; Pneumococcal Vaccines*; Meningococcal Vaccines*
  16. 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; Viral Vaccines/administration & dosage; Viral Vaccines/immunology*
  17. Fulltext Efficacy and long-term safety of a dengue vaccine in regions of endemic disease
    Hadinegoro SR, Arredondo-García JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, et al.
    N Engl J Med, 2015 Sep 24;373(13):1195-206.
    PMID: 26214039 DOI: 10.1056/NEJMoa1506223
    BACKGROUND: A candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries. We report the results of long-term follow-up interim analyses and integrated efficacy analyses.
    METHODS: We are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials, CYD14 and CYD15, and a phase 2b trial, CYD23/57. We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15.
    RESULTS: Follow-up data were available for 10,165 of 10,275 participants (99%) in CYD14 and 19,898 of 20,869 participants (95%) in CYD15. Data were available for 3203 of the 4002 participants (80%) in the CYD23 trial included in CYD57. During year 3 in the CYD14, CYD15, and CYD57 trials combined, hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group. Pooled relative risks of hospitalization for dengue were 0.84 (95% confidence interval [CI], 0.56 to 1.24) among all participants, 1.58 (95% CI, 0.83 to 3.02) among those under the age of 9 years, and 0.50 (95% CI, 0.29 to 0.86) among those 9 years of age or older. During year 3, hospitalization for severe dengue, as defined by the independent data monitoring committee criteria, occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group. Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3% (95% CI, 55.7 to 64.5) for all participants, 65.6% (95% CI, 60.7 to 69.9) for those 9 years of age or older, and 44.6% (95% CI, 31.6 to 55.0) for those younger than 9 years of age.
    CONCLUSIONS: Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term follow-up, the risk among children 2 to 16 years of age was lower in the vaccine group than in the control group. (Funded by Sanofi Pasteur; ClinicalTrials.gov numbers, NCT00842530, NCT01983553, NCT01373281, and NCT01374516.).
    Matched MeSH terms: Vaccines, Attenuated/adverse effects; Vaccines, Attenuated/immunology; Dengue Vaccines/adverse effects; Dengue Vaccines/immunology*
  18. Cost Effectiveness of Pneumococcal Vaccination in Children in Low- and Middle-Income Countries: A Systematic Review
    Saokaew S, Rayanakorn A, Wu DB, Chaiyakunapruk N
    Pharmacoeconomics, 2016 12;34(12):1211-1225.
    PMID: 27510721
    BACKGROUND: Although pneumococcal conjugate vaccines (PCVs) have been available for prevention of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae (S. pneumoniae) for over a decade, their adoption into national immunization programmes in low- and middle-income countries (LMICs) is still limited. Economic evaluations (EEs) play a crucial role in support of evidence-informed decisions.

    OBJECTIVE: This systematic review aims to provide a critical summary of EEs of PCVs and identify key drivers of EE findings in LMICs.

    METHODS: We searched Scopus, ISI Web of Science, PubMed, Embase and Cochrane Central from their inception to 30 September 2015 and limited the search to LMICs. The search was undertaken using the search strings 'pneumococc* AND conjugat* AND (vaccin* OR immun*)' AND 'economic OR cost-effectiveness OR cost-benefit OR cost-utility OR cost-effectiveness OR cost-benefit OR cost-utility' in the abstract, title or keyword fields. To be included, each study had to be a full EE of a PCV and conducted for an LMIC. Studies were extracted and reviewed by two authors. The review involved standard extraction of the study overview or the characteristics of the study, key drivers or parameters of the EE, assumptions behind the analyses and major areas of uncertainty.

    RESULTS: Out of 134 records identified, 22 articles were included. Seven studies used a Markov model for analysis, while 15 studies used a decision-tree analytic model. Eighteen studies performed a cost-utility analysis (CUA), with disability-adjusted life-years, quality-adjusted life-years or life-years gained as a measure of health outcome, while four studies focused only on cost-effectiveness analysis (CEA). Both CEA and CUA findings were provided by eight studies. Herd effects and serotype replacement were considered in 10 and 13 studies, respectively. The current evidence shows that both the 10-valent and 13-valent PCVs are probably cost effective in comparison with the 7-valent PCV or no vaccination. The most influential parameters were vaccine efficacy and coverage (in 16 of 22 studies), vaccine price (in 13 of 22 studies), disease incidence (in 11 of 22 studies), mortality from IPD and pneumonia (in 8 of 22 studies) and herd effects (in 4 of 22 studies). The findings were found to be supportive of the products owned by the manufacturers.

    CONCLUSION: Our review demonstrated that an infant PCV programme was a cost-effective intervention in most LMICs (in 20 of 22 studies included). The results were sensitive to vaccine efficacy, price, burden of disease and sponsorship. Decision makers should consider EE findings and affordability before adoption of PCVs.

    Matched MeSH terms: Vaccines, Conjugate/administration & dosage; Vaccines, Conjugate/economics; Pneumococcal Vaccines/administration & dosage*; Pneumococcal Vaccines/economics
  19. Fulltext Nanoparticles in influenza subunit vaccine development: Immunogenicity enhancement
    Khalaj-Hedayati A, Chua CLL, Smooker P, Lee KW
    Influenza Other Respir Viruses, 2020 Jan;14(1):92-101.
    PMID: 31774251 DOI: 10.1111/irv.12697
    The threat of novel influenza infections has sparked research efforts to develop subunit vaccines that can induce a more broadly protective immunity by targeting selected regions of the virus. In general, subunit vaccines are safer but may be less immunogenic than whole cell inactivated or live attenuated vaccines. Hence, novel adjuvants that boost immunogenicity are increasingly needed as we move toward the era of modern vaccines. In addition, targeting, delivery, and display of the selected antigens on the surface of professional antigen-presenting cells are also important in vaccine design and development. The use of nanosized particles can be one of the strategies to enhance immunogenicity as they can be efficiently recognized by antigen-presenting cells. They can act as both immunopotentiators and delivery system for the selected antigens. This review will discuss on the applications, advantages, limitations, and types of nanoparticles (NPs) used in the preparation of influenza subunit vaccine candidates to enhance humoral and cellular immune responses.
    Matched MeSH terms: Influenza Vaccines/administration & dosage; Influenza Vaccines/immunology*; Vaccines, Subunit/administration & dosage; Vaccines, Subunit/immunology*
  20. 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*; Vaccines, Synthetic/administration & dosage; Vaccines, Synthetic/genetics; Vaccines, Synthetic/immunology
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