Displaying publications 1 - 20 of 89 in total

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  1. Nagendrakumar SB, Hong NT, Geoffrey FT, Jacqueline MM, Andrew D, Michelle G, et al.
    Vaccine, 2015 Aug 26;33(36):4513-9.
    PMID: 26192355 DOI: 10.1016/j.vaccine.2015.07.014
    Pigs play a significant role during outbreaks of foot-and-mouth disease (FMD) due to their ability to amplify the virus. It is therefore essential to determine what role vaccination could play to prevent clinical disease and lower virus excretion into the environment. In this study we investigated the efficacy of the double oil emulsion A Malaysia 97 vaccine (>6PD50/dose) against heterologous challenge with an isolate belonging to the A SEA-97 lineage at 4 and 7 days post vaccination (dpv). In addition, we determined whether physical separation of pigs in the same room could prevent virus transmission. Statistically there was no difference in the level of protection offered by 4 and 7 dpv. However, no clinical disease or viral RNA was detected in the blood of pigs challenged 4 dpv, although three of the pigs had antibodies to the non-structural proteins (NSPs), indicating viral replication. Viral RNA was also detected in nasal and saliva swabs, but on very few occasions. Two of the pigs vaccinated seven days prior to challenge had vesicles distal from the injection site, but on the inoculated foot, and two pigs had viral RNA detected in the blood. One pig sero-converted to the NSPs. In contrast, all unvaccinated and inoculated pigs had evidence of infection. No infection occurred in any of the susceptible pigs in the same room, but separated from the infected pigs, indicating that strict biosecurity measures were sufficient under these experimental conditions to prevent virus transmission. However, viral RNA was detected in the nasal swabs of one group of pigs, but apparently not at sufficient levels to cause clinical disease. Vaccination led to a significant decrease in viral RNA in vaccinated pigs compared to unvaccinated and infected pigs, even with this heterologous challenge, and could therefore be considered as a control option during outbreaks.
  2. Lohr V, Genzel Y, Behrendt I, Scharfenberg K, Reichl U
    Vaccine, 2010 Aug 31;28(38):6256-64.
    PMID: 20638458 DOI: 10.1016/j.vaccine.2010.07.004
    An adherently growing MDCK cell line was adapted in a two-step process in a fully defined medium and in suspension. The resulting MDCK.SUS2 cells were subsequently evaluated for their potential as host cells for influenza vaccine production in two lab-scale bioreactors (wave and stirred-tank). Cell concentrations up to 2.3 x 10(6)cells/mL were obtained after 96 h, which is slightly higher than cell concentrations obtained with adherent MDCK cells cultivated on microcarriers (2g/L). Infections with influenza A/PR/8/34 and B/Malaysia resulted in high virus titers (2.90 and 2.75 log HA units/100 microL, respectively). The monitoring of extracellular metabolites, including amino acids, revealed a change in some of the metabolite consumption or release profiles, which indicates changes in metabolism during the adaptation process. Overall, the MDCK.SUS2 cell line represents a new cell substrate for a robust influenza vaccine production in a fully defined process.
  3. Sagara I, Dicko A, Ellis RD, Fay MP, Diawara SI, Assadou MH, et al.
    Vaccine, 2009 May 18;27(23):3090-8.
    PMID: 19428923 DOI: 10.1016/j.vaccine.2009.03.014
    A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel. Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000/microL/day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.
  4. Harapan H, Wagner AL, Yufika A, Setiawan AM, Anwar S, Wahyuni S, et al.
    Vaccine, 2020 10 07;38(43):6800-6806.
    PMID: 32861468 DOI: 10.1016/j.vaccine.2020.08.034
    BACKGROUND: A clinical trial is ongoing to evaluate the safety and efficacy of a monkeypox vaccine among healthcare workers (HCWs). The critical question that needs to be addressed is whether HCWs are willing to accept and purchase this vaccine. The objective of this study was to evaluate the acceptance and willingness to pay (WTP) for the vaccine among HCWs.

    METHODS: From May to July 2019, a cross-sectional study was conducted among registered general practitioners (GPs) in Indonesia. A contingent valuation method was employed to evaluate the WTP. Besides acceptance and WTP, various explanatory variables were also collected and assessed. A logistic regression and a multivariable linear regression were used to explore the explanatory variables influencing acceptance and WTP, respectively.

    RESULTS: Among 407 respondents, 391 (96.0%) expressed acceptance of a free vaccination. The mean and median WTP was US$ 37.0(95%CI:US$ 32.76-US$ 41.23) and US$ 17.90(95%CI:US$ 17.90-US$ 17.90), respectively. In an unadjusted analysis, those 30 years old or younger had 2.94 times greater odds of vaccine acceptance compared to those who were older (95%CI: 1.07-8.08). Location of alma mater, type of workplace, length of individual medical experience, and monthly income of GPs were all significantly associated with WTP.

    CONCLUSION: Although the vast majority of GPs would accept a freely provided vaccine, they were also somewhat price sensitive. This finding indicates that partial subsidy maybe required to achieve high vaccine coverage, particularly among GPs at community health centres or those with a shorter duration of medical practice.

  5. Camilloni B, Neri M, Lepri E, Basileo M, Sigismondi N, Puzelli S, et al.
    Vaccine, 2010 Nov 3;28(47):7536-41.
    PMID: 20846530 DOI: 10.1016/j.vaccine.2010.08.064
    The study evaluated the immunogenicity and efficacy of a trivalent subunit MF59-adjuvanted influenza vaccine (A/Wisconsin/67/05 (H3N2), A/Solomon Islands/3/06 (H1N1) and B/Malaysia/2506/04) in preventing serologically diagnosed infections in a group of 67 institutionalized elderly volunteers during 2007/2008 winter, characterized by co-circulation of drifted A/H3N2, A/H1N1 and B influenza viruses. Influenza vaccination induced a significant increase in the amounts of hemagglutination inhibiting antibodies, both against the vaccine and the epidemic drifted strains. However, vaccination did not prevent the circulation of the new drifted influenza B virus (B/Florida/4/06-like), belonging to the B/Yamagata/16/88-lineage, antigenically and genetically distinct from B/Victoria/2/87-lineage viruses from which the vaccine B strain was derived.
  6. Siddiqui A, Ahmed A, Tanveer M, Saqlain M, Kow CS, Hasan SS
    Vaccine, 2021 08 31;39(37):5251-5253.
    PMID: 34364719 DOI: 10.1016/j.vaccine.2021.07.072
  7. Wong LP, Alias H, Hassan J, AbuBakar S
    Vaccine, 2017 10 13;35(43):5912-5917.
    PMID: 28886944 DOI: 10.1016/j.vaccine.2017.08.074
    The aim of this study was to examine the willingness of pregnant women to have prenatal screening for the Zika virus (ZIKV). Secondly, the study also assessed the acceptability of a hypothetical Zika vaccination and its association with the health belief model (HBM) constructs. A cross-sectional study was conducted from 4th October to 11th November 2016, among pregnant women who attended antenatal care at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The majority (81.8%) was willing to be tested for ZIKV and 78% felt that their spouse would be willing to be tested for ZIKV. A total of 94% expressed a willingness to receive a Zika vaccination if available. The participants expressed high perceived benefits of a ZIKV vaccination. Although many have a high perception of the severity of ZIKV, the proportion with a strong perception of their susceptibility to ZIKV was low. In the multivariate analysis of all the HBM constructs, cue-to-action, namely physician recommendation (odds ratio [OR]=2.288; 95% confidence interval [CI] 1.093-4.793) and recommendation from friends or relatives (OR=4.030; 95% CI 1.694-9.587), were significantly associated with a willingness to be vaccinated against ZIKV. The favourable response to a Zika vaccination implies that more research attention has to be given to develop a vaccine against ZIKV. Should the vaccine be available in the future, publicity and healthcare providers would play a vital role in ensuring vaccine uptake among pregnant women.
  8. Palaniappan PA, Mohamed Sukur S, Liow YL, Maniam S, Sherina F, Ahmad N
    Vaccine, 2020 12 03;38(51):8232-8237.
    PMID: 33139134 DOI: 10.1016/j.vaccine.2020.09.066
    BACKGROUND: Haemophilus influenzae (H. influenzae) is a human upper respiratory tract colonizer which causes wide range of disease especially in children<5 years old and in the elderly. Although worldwide incidence in industrialised countries where Hib vaccination is commonly used has dropped sharply since implementation of H. influenzae type b (Hib) vaccination, there is limited data on the disease burden caused by H. influenzae in Malaysia post vaccination era. A change in predominant serotype from type b to non-b serotypes of H. influenzae in invasive diseases was reported worldwide. We investigated the carriage of H. influenzae post vaccination era among 2-4 years old.

    METHODOLOGY: Randomly, we collected 436 oropharyngeal swabs from healthy children aged 2-4 years in 30 registered childcare centres in Kuala Lumpur (August 2018-May 2019). Informed consent and written questionnaires were obtained from parents. H. influenzae was identified by standard microbiological methods. Univariable analysis was carried out to describe variables associated with colonization. All variables with p 

  9. Khan TM, Sahibzada MU
    Vaccine, 2016 Apr 19;34(18):2074-81.
    PMID: 26993330 DOI: 10.1016/j.vaccine.2016.03.008
    A qualitative study design was adapted to explore the challenges faced by health workers (HWs) during the polio health campaign. In addition, HWs' opinions about the factors causing parents to refuse oral polio vaccination (OPV) were also explored. Four focus group discussions (FGDs) were held (from 1st January 2015-31st March 2015) with the HWs who participated in the OPV campaigns in the polio red zones of Khyber Pakhtoon Khawa (KPK) province of Pakistan, namely Kohat (FG 1), Domel and Bannu (FG 2), Hangoo (FG 3), and Peshawar (FG 4). A total of N=42 HWs (10-11 in each FG) agreed to participate in this study. Overall, HWs disclosed that public attitude and harsh behaviour towards the HWs and security threats are the two main challenges they face. Common issues hindering parents' willingness to vaccinate their children against OPV are: OPV is seen as haram and not permitted in Islam, it is said to contain the blood of pigs (Khinzir) and monkeys, and parents are afraid that it is done to induce sterility among their children. HWs also shared that parents have a strong belief in the conspiracies that are associated with OPV, i.e. the USA and CIA, are spying on us and our government is helping them to achieve their agenda. Furthermore, HWs revealed that frequent visits may further strengthen parents' perceptions and make them more resistant to OPV. The common side effects of OPV reported by parents were mainly gastro-intestinal problems and in some cases mild to moderate fever with some respiratory symptoms. There is a great need to improve the logistics and facilities for HWs assisting in vaccination programmes. Furthermore, it is necessary to improve education, so people understand the basic concept of revaccination and booster doses, thereby assisting in creating a basic understanding of vaccinations, which may trigger changes in attitudes and make people believe in the benefits of OPV rather than following the conspiracies that lead them to refuse it.
    Matched MeSH terms: Poliovirus Vaccine, Oral/administration & dosage*
  10. Kim SH, Chung DR, Song JH, Baek JY, Thamlikitkul V, Wang H, et al.
    Vaccine, 2020 08 27;38(38):6065-6073.
    PMID: 31590932 DOI: 10.1016/j.vaccine.2019.09.065
    This study was performed to investigate the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae in Asian countries. A prospective surveillance study on S. pneumoniae collected from adult patients (≥50 years old) with invasive pneumococcal disease or community-acquired pneumonia was performed at 66 hospitals in Asian countries (Korea, China, Malaysia, Singapore, the Philippines, and Thailand) in 2012-2017. Serotyping and antimicrobial susceptibility tests of 850 pneumococcal isolates were performed. The proportions of isolates with serotypes covered by 13-valent pneumococcal conjugate vaccine (PCV13) were 37.0% in Korea, 53.4% in China, 77.2% in Malaysia, 35.9% in the Philippines, 68.7% in Singapore, and 60.2% in Thailand. Major serotypes were 19F (10.4%), 19A (10.1%), and 3 (8.5%) in 2012-2017, with different serotype distributions in each country. Macrolide resistance in pneumococci was high (66.8%) and prevalence of multidrug resistance (MDR) also remained high (50.8%). MDR non-PCV13 serotypes such as 11A, 15A, 35B, and 23A have emerged in Asian countries. This study showed the persistent prevalence of 19F and 19A with a noteworthy increase of certain non-PCV13 serotypes in Asian countries. High prevalence of macrolide resistance and MDR was also found in pneumococcal isolates. These data emphasize the need for continued surveillance of pneumococcal epidemiology in Asia in the post-pneumococcal vaccine era.
  11. Alfelali M, Barasheed O, Tashani M, Azeem MI, El Bashir H, Memish ZA, et al.
    Vaccine, 2015 May 21;33(22):2562-9.
    PMID: 25887084 DOI: 10.1016/j.vaccine.2015.04.006
    Influenza is an important health hazard among Hajj pilgrims. For the last ten years, pilgrims are being recommended to take influenza vaccine before attending Hajj. Vaccination coverage has increased in recent years, but whether there has been any change in the prevalence of influenza-like illness (ILI) is not known. In this analysis, we examined the changes in the rate of ILI against seasonal influenza vaccine uptake among Hajj pilgrims over the last decade.
  12. Lopez AL, Dutta S, Qadri F, Sovann L, Pandey BD, Bin Hamzah WM, et al.
    Vaccine, 2020 02 29;38 Suppl 1:A18-A24.
    PMID: 31326255 DOI: 10.1016/j.vaccine.2019.07.035
    INTRODUCTION: Although the current pandemic of cholera originated in Asia, reports of cholera cases and outbreaks in the region are sparse. To provide a sub-regional assessment of cholera in South and Southeast Asia, we collated published and unpublished data from existing surveillance systems from Bangladesh, Cambodia, India, Malaysia, Nepal, Pakistan, Philippines, Thailand and Vietnam.

    METHODS: Data from existing country surveillance systems on diarrhea, acute watery diarrhea, suspected cholera and/or confirmed cholera in nine selected Asian countries (Bangladesh, Cambodia, India, Malaysia, Nepal, Pakistan, Philippines, Thailand and Vietnam) from 2011 to 2015 (or 2016, when available) were collated. We reviewed annual cholera reports from WHO and searched PubMed and/or ProMED to complement data, where information is not completely available.

    RESULTS: From 2011 to 2016, confirmed cholera cases were identified in at least one year of the 5- or 6-year period in the countries included. Surveillance for cholera exists in most countries, but cases are not always reported. India reported the most number of confirmed cases with a mean of 5964 cases annually. The mean number of cases per year in the Philippines, Pakistan, Bangladesh, Malaysia, Nepal and Thailand were 760, 592, 285, 264, 148 and 88, respectively. Cambodia and Vietnam reported 51 and 3 confirmed cholera cases in 2011, with no subsequent reported cases.

    DISCUSSION AND CONCLUSION: We present consolidated results of available surveillance in nine Asian countries and supplemented these with publication searches. There is paucity of readily accessible data on cholera in these countries. We highlight the continuing existence of the disease even in areas with improved sanitation and access to safe drinking water. Continued vigilance and improved surveillance in countries should be strongly encouraged.

  13. Wu DB, Chaiyakunapruk N, Chong HY, Beutels P
    Vaccine, 2015 Mar 30;33(14):1633-58.
    PMID: 25681663 DOI: 10.1016/j.vaccine.2015.01.081
    BACKGROUND: Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs ("PCV10" and "PCV13"). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch.
    OBJECTIVE: This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006.
    METHODS: We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies.
    RESULTS: Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study.
    CONCLUSION: A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer.
    KEYWORDS: Cost-effectiveness; Cost–benefit; Pneumococcal conjugate vaccine; Streptococcus pneumoniae
    Matched MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine/economics*
  14. Kim H, Schoofs P, Anderson DA, Tannock GA, Rockman SP
    Vaccine, 2014 May 1;32(21):2474-9.
    PMID: 24631096 DOI: 10.1016/j.vaccine.2014.02.079
    Gene reassortment has proved useful in improving yields of influenza A antigens of egg-based inactivated vaccines, but similar approaches have been difficult with influenza B antigens. Current regulations for influenza vaccine seed viruses limit the number of egg passages and as a result resultant yields from influenza B vaccine seed viruses are frequently inconsistent. Therefore, reliable approaches to enhance yields of influenza B vaccine seed viruses are required for efficient vaccine manufacture. In the present study three stable cold-adapted (ca) mutants, caF, caM and caB derived from seasonal epidemic strains, B/Florida/4/2006, B/Malaysia/2506/2004 and B/Brisbane/60/2008 were prepared, which produced high hemagglutinin antigen yields and also increased viral yields of reassortants possessing the desired 6:2 gene constellation. The results demonstrate that consistent improvements in yields of influenza B viruses can be obtained by cold adaptation following extended passage. Taken together, the three ca viruses were shown to have potential as donor viruses for the preparation of high-yielding influenza B vaccine viruses by reassortment.
  15. Harapan H, Mudatsir M, Yufika A, Nawawi Y, Wahyuniati N, Anwar S, et al.
    Vaccine, 2019 03 07;37(11):1398-1406.
    PMID: 30739794 DOI: 10.1016/j.vaccine.2019.01.062
    BACKGROUND: Understanding people's perceptions of the economic benefits of a potential Zika vaccine (ZV) is critical to accelerating its introduction into either public sector programs or private market. The aim of this study was to assess the acceptance and willingness-to-pay (WTP) for a hypothetical ZV and the associated explanatory variables in Indonesia.

    METHODS: We conducted a health facility-based cross-sectional study in Aceh and West Sumatra province from 1 February to 13 June 2018. Patients who visited outpatient departments, have had children or were expecting their first child, were approached and interviewed to collect information on acceptance, WTP, demographic and socio-economic variables and attitudes towards childhood vaccines. Associations of explanatory variables influencing acceptance and WTP were assessed using logistic regression and linear regression analysis, respectively.

    RESULTS: In total, 956 respondents were included in the final analysis of acceptance, of whom 338 (35.3%) expressed their WTP. We found that 757 (79.1%) of the respondents were likely to be vaccinated and to recommend their partner to be vaccinated. Higher educational attainment, having a job, having heard about Zika and a good attitude towards childhood vaccination were associated with ZV acceptance in the univariate analyses. In the multivariate analysis, attitude towards childhood vaccination was the strongest predictor for ZV vaccination. We found the geometric mean and median of WTP was US$ 13.1 (95% CI: 11.37-15.09) and US$ 7.0 (95% CI: 4.47-10.98), respectively. In the final model, having heard about Zika, having a job, and higher income were associated with a higher WTP.

    CONCLUSION: Although the acceptance rate of the ZV is relatively high in Indonesia, less than 40% of respondents are willing to pay, underscoring the need for a low-cost, high-quality vaccine and public sector subsidies for Zika vaccinations in the country.

  16. Hussain AI, Cordeiro M, Sevilla E, Liu J
    Vaccine, 2010 May 14;28(22):3848-55.
    PMID: 20307595 DOI: 10.1016/j.vaccine.2010.03.005
    Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable.
  17. Snider CJ, Boualam L, Tallis G, Takashima Y, Abeyasinghe R, Lo YR, et al.
    Vaccine, 2023 Apr 06;41 Suppl 1:A58-A69.
    PMID: 35337673 DOI: 10.1016/j.vaccine.2022.02.022
    Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.
    Matched MeSH terms: Poliovirus Vaccine, Oral/adverse effects
  18. Ravichandran M, Ali SA, Rashid NH, Kurunathan S, Yean CY, Ting LC, et al.
    Vaccine, 2006 May 1;24(18):3750-61.
    PMID: 16102875
    In this paper, we describe the development of VCUSM2, a live metabolic auxotroph of Vibrio cholerae O139. Auxotrophy was achieved by mutating a house keeping gene, hemA, that encodes for glutamyl-tRNA reductase, an important enzyme in the C5 pathway for delta-aminolevulenic acid (ALA) biosynthesis, which renders this strain dependent on exogenous ALA for survival. Experiments using the infant mouse and adult rabbit models show that VCUSM2 is a good colonizer of the small intestine and elicits greater than a four-fold rise in vibriocidal antibodies in vaccinated rabbits. Rabbits vaccinated with VCUSM2 were fully protected against subsequent challenge with 1 x 10(11) CFU of the virulent wild type (WT) strain. Experiments using ligated ileal loops of rabbits show that VCUSM2 is 2.5-fold less toxic at the dose of 1 x 10(6) CFU compared to the WT strain. Shedding of VCUSM2 in rabbits were found to occur for no longer than 4 days and its maximum survival rate in environmental waters is 8 days compared to the greater than 20 days for the WT strain. VCUSM2 is thus a potential vaccine candidate against infection by V. cholerae O139.
  19. Zeng W, Halasa-Rappel YA, Baurin N, Coudeville L, Shepard DS
    Vaccine, 2018 01 08;36(3):413-420.
    PMID: 29229427 DOI: 10.1016/j.vaccine.2017.11.064
    Following publication of results from two phase-3 clinical trials in 10 countries or territories, endemic countries began licensing the first dengue vaccine in 2015. Using a published mathematical model, we evaluated the cost-effectiveness of dengue vaccination in populations similar to those at the trial sites in those same Latin American and Asian countries. Our main scenarios (30-year horizon, 80% coverage) entailed 3-dose routine vaccinations costing US$20/dose beginning at age 9, potentially supplemented by catch-up programs of 4- or 8-year cohorts. We obtained illness costs per case, dengue mortality, vaccine wastage, and vaccine administration costs from the literature. We estimated that routine vaccination would reduce yearly direct and indirect illness cost per capita by 22% (from US$10.51 to US$8.17) in the Latin American countries and by 23% (from US$5.78 to US$4.44) in the Asian countries. Using a health system perspective, the incremental cost-effectiveness ratio (ICER) averaged US$4,216/disability-adjusted life year (DALY) averted in the five Latin American countries (range: US$666/DALY in Puerto Rico to US$5,865/DALY in Mexico). In the five Asian countries, the ICER averaged US$3,751/DALY (range: US$1,935/DALY in Malaysia to US$5,101/DALY in the Philippines). From a health system perspective, the vaccine proved to be highly cost effective (ICER under one times the per capita GDP) in seven countries and cost effective (ICER 1-3 times the per capita GDP) in the remaining three countries. From a societal perspective, routine vaccination proved cost-saving in three countries. Including catch-up campaigns gave similar ICERs. Thus, this vaccine could have a favorable economic value in sites similar to those in the trials.
  20. Kim T, Hong JK, Oem JK, Lee KN, Lee HS, Kim YJ, et al.
    Vaccine, 2019 03 14;37(12):1702-1709.
    PMID: 30712811 DOI: 10.1016/j.vaccine.2018.11.080
    After massive foot-and-mouth disease (FMD) outbreaks originated from Jincheon County from Dec. 2014 to Apr. 2015, the effectiveness of the previous FMD vaccine containing only the O1 Manisa as the O antigen, O1 Manisa + A Malaysia 97 + Asia 1 Sharmir trivalent vaccine, was questioned in South Korea, and a change in the O antigen in FMD vaccines was demanded to control the FMD caused by FMDV O/Jincheon/SKR/2014, the O Jincheon strain. Therefore, the efficacies of O1 Manisa + O 3039 bivalent vaccine and O 3039 monovalent vaccine were studied for cross-protection against heterologous challenge with the O Jincheon strain. In this study, the efficacy of the O1 Manisa + O 3039 bivalent vaccine was better than that of the O 3039 monovalent vaccine, even though the serological relationship (r1 value) between O Jincheon and O 3039 was matched according to the OIE Terrestrial Manual. According to serological test results from vaccinated specific pathogen free pigs, virus neutralization test titers against Jincheon were good estimates for predicting protection against challenge. A field trial of the O1 Manisa + O 3039 bivalent vaccine was performed to estimate the possibility of field application in conventional pig farms, especially due to concerns about the effect of maternally derived antibodies (MDA) in field application of the FMD vaccine. According to the result of the field trial, the O1 Manisa + O 3039 bivalent vaccine was considered to overcome MDA. The results of the efficacy and field trials indicated that the O1 Manisa + O3039 vaccine could be suitable to replace previous FMD vaccines to control the FMD field situation caused by O Jincheon FMDV.
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