Displaying publications 41 - 60 of 89 in total

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  1. Lam SK, Burke D, Capeding MR, Chong CK, Coudeville L, Farrar J, et al.
    Vaccine, 2011 Nov 28;29(51):9417-22.
    PMID: 21864627 DOI: 10.1016/j.vaccine.2011.08.047
    Infection with dengue virus is a major public health problem in the Asia-Pacific region and throughout tropical and sub-tropical regions of the world. Vaccination represents a major opportunity to control dengue and several candidate vaccines are in development. Experts in dengue and in vaccine introduction gathered for a two day meeting during which they examined the challenges inherent to the introduction of a dengue vaccine into the national immunisation programmes of countries of the Asia-Pacific. The aim was to develop a series of recommendations to reduce the delay between vaccine licensure and vaccine introduction. Major recommendations arising from the meeting included: ascertaining and publicising the full burden and cost of dengue; changing the perception of dengue in non-endemic countries to help generate global support for dengue vaccination; ensuring high quality active surveillance systems and diagnostics; and identifying sustainable sources of funding, both to support vaccine introduction and to maintain the vaccination programme. The attendees at the meeting were in agreement that with the introduction of an effective vaccine, dengue is a disease that could be controlled, and that in order to ensure a vaccine is introduced as rapidly as possible, there is a need to start preparing now.
  2. Lee MHP, Tan CW, Tee HK, Ong KC, Sam IC, Chan YF
    Vaccine, 2021 03 19;39(12):1708-1720.
    PMID: 33640144 DOI: 10.1016/j.vaccine.2021.02.024
    Enterovirus A71 (EV-A71) causes hand, foot and mouth disease (HFMD) in young children. It is associated with severe neurological complications and death. This study aims to develop a live-attenuated vaccine by codon deoptimization (CD) and codon-pair deoptimization (CPD) of EV-A71. CD is generated by introducing the least preferred codons for amino acids while CPD increases the presence of underrepresented codon pairs in the specific genes. CD and CPD chimeras were generated by synonymous mutations at the VP2, VP3, VP1 and 2A gene regions, designated as XYZ. All twelve deoptimized viruses were viable with similar replication kinetics, but the plaque sizes were inversely proportional to the level of deoptimization. All the deoptimized viruses showed attenuated growth in vitro with reduced viral protein expression at 48 h and lower viral RNA at 39 °C. Six-week-old ICR mice were immunized intraperitoneally with selected CD and CPD X and XY vaccine candidates covering the VP2-VP3 and VP2-VP3-VP1 genes, respectively. All vaccine candidates elicited high anti-EV-A71 IgG levels similar to wild-type (WT) EV-A71. The CD X and CPD X vaccines produced robust neutralizing antibodies but not the CD XY and CPD XY. On lethal challenge, offspring of mice immunized with WT, CD X and CPD X were fully protected, but the CD XY- and CPD XY-vaccinated mice had delayed symptoms and eventually died. Similarly, active immunization of 1-day-old suckling mice with CD X, CPD X and CD XY vaccine candidates provided complete immune protection but CPD XY only protected 40% of the challenged mice. Histology of the muscles from CD X- and CPD X-vaccinated mice showed minimal pathology compared to extensive inflammation in the post-challenged mock-vaccinated mice. Overall, we demonstrated that the CD X and CPD X elicited good neutralizing antibodies, conferred immune protection and are promising live-attenuated vaccine candidates for EV-A71.
  3. Lee SY, Park ME, Kim RH, Ko MK, Lee KN, Kim SM, et al.
    Vaccine, 2015 Jan 29;33(5):664-9.
    PMID: 25528521 DOI: 10.1016/j.vaccine.2014.12.007
    Of the seven known serotypes of foot-and-mouth disease virus (FMDV), type A has the most diverse variations. Genetic variations also occur frequently at VP1, VP2, VP3, and VP4 because these proteins constitute the viral capsid. The structural proteins of FMDV, which are closely related to immunologic correlations, are the most easily analyzed because they have highly accessible information. In this study we analyzed the type A vaccine viruses by alignment of available sequences in order to find appropriate vaccine strains. The matching rate of ASIA topotype-specific sites (20 amino acids) located on the viral surface, which are mainly VP1 and VP2, was highly related to immunologic reactivity. Among the available vaccines analyzed in this study, we suggest that A Malaysia 97 could be used as a vaccine virus as it has the highest genetic similarity and immunologic aspects to field strains originating in East Asia.
  4. Lim AH, Ab Rahman N, Ong SM, Paraja J, Rashid R, Parmar IS, et al.
    Vaccine, 2022 Sep 16;40(39):5675-5682.
    PMID: 36030123 DOI: 10.1016/j.vaccine.2022.08.032
    There is a notable lack of vaccine effectiveness studies using test-negative case-controlled approach in low- and middle-income countries which have different logistic, demographic and socio-economic conditions from high-income countries. We aimed to estimate the effectiveness of BNT162b2 vaccine against COVID-19 infection over time, intensive care unit admission, severe or critical disease and death due to COVID-19. This study was conducted in the resident population of Labuan aged ≥18 years who had been tested for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction between 1 March 2021 and 31 October 2021. We used a test-negative case-control design where 2644 pairs of cases and controls were matched by age, sex, testing date, nationality and testing reason. Analysis was stratified by age group to estimate age effect (<60 years and ≥60 years). Of 22217 individuals tested by Reverse-Transcriptase Polymerase Chain Reaction, 5100 were positive for SARS-CoV-2 and aged 18 years and above. Overall vaccine effectiveness ≥ 14 days after the second dose was 65.2% (95% CI: 59.8-69.9%) against COVID-19 infection, 92.5% (95% CI: 72.3-98.8%) against intensive care unit admission, and 96.5% (95% CI: 82.3-99.8%) against COVID-19 deaths. Among infected individuals, vaccine effectiveness was 79.2% (95% CI: 42.3-94.1%) in preventing severe or critical disease due to COVID-19. Vaccine effectiveness for ≥60 years was 72.3% (95% CI: 53.4-83.9%) in fully vaccinated individuals, higher than 64.8% (95% CI: 49.3-59.1%) for those <60 years. Two doses of BNT162b2 were highly effective against COVID-19 infection, severe or critical disease, intensive care unit admission and death due to COVID-19. This study addresses a gap in literature on BNT162b2 vaccine effectiveness in low- and middle-income populations and demonstrates the feasibility of such a study design in a resource limited setting while supporting evidence of waning immunity.
  5. Lim PY, Hickey AC, Jamiluddin MF, Hamid S, Kramer J, Santos R, et al.
    Vaccine, 2015 Nov 4;33(44):6017-24.
    PMID: 26271825 DOI: 10.1016/j.vaccine.2015.05.108
    A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like-particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime-boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 μg/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71.
  6. Lin Y, Lin Z, He F, Hu Z, Zimet GD, Alias H, et al.
    Vaccine, 2019 10 16;37(44):6714-6723.
    PMID: 31548016 DOI: 10.1016/j.vaccine.2019.09.026
    BACKGROUND: Little research has been conducted on the intention to obtain HPV vaccine now that the vaccine is approved for use in China. Acceptance of the three HPV vaccines, which differ in valency and price, has never been investigated.

    METHODS: An online cross-sectional survey assessing female undergraduate students' intention to obtain the HPV vaccine and their acceptability of 2-, 4- and 9-valent HPV vaccines (2vHPV, 4vHPV, and 9vHPV, respectively).

    RESULTS: Of a total of 997 complete responses, 55.2% reported intent to obtain the HPV vaccine. Some of the significant factors exerting influence on intent to obtain HPV vaccination were high knowledge score (OR = 1.469, 95% CI:1.087-1.987), perceived high risk of HPV infection (OR = 1.466, 95%CI:1.017-2.114), perception of no serious side effects (OR = 1.562, 95%CI:1.150-2.121), and mass media exposure to HPV vaccination information (OR = 2.196, 95%CI: 1.625-2.966). Socioeconomic status indicators did not significantly influence intent to obtain the HPV vaccine. A higher proportion of respondents were willing to pay for 2vHPV (78.6%) and 4vHPV (68.0%) compared with 9vHPV (49.3%). Socioeconomic status indicators were the strongest correlates of acceptability for all the three vaccines. Exposure to mass media reporting about HPV vaccination is the factor which exerts the most influence on acceptance of 9vHPV after socioeconomic status indicators.

    CONCLUSIONS: It is important to improve knowledge and health beliefs, and to establish a mass media marketing strategy to promote HPV vaccination in order to enhance HPV vaccine uptake. Undergraduate female students should be provided with detailed information about the different valency vaccine choices to help them make informed decisions about immunization.

  7. Lin Y, Lin Z, He F, Chen H, Lin X, Zimet GD, et al.
    Vaccine, 2020 03 23;38(14):3021-3030.
    PMID: 32127227 DOI: 10.1016/j.vaccine.2020.02.042
    OBJECTIVE: This study aims to investigate acceptance and willingness to pay for HPV vaccination among adult women in China.

    METHODS: An online survey was sent to mothers aged 27-45 years of primary school pupils in the Fujian province, China. Participants completed questions about HPV related knowledge and health beliefs, intention to take the HPV vaccine and the willingness to pay for bivalent vaccine (2vHPV), quadrivalent vaccine (4vHPV), and 9-valent HPV vaccine (9vHPV).

    RESULTS: Of a total of 2339 complete responses, 58.3% reported intent to obtain HPV vaccine. Mothers who were younger in age, residing in urban, working in managerial or professional occupations, who knew someone with cervical cancer and who were able to make independent decisions about the HPV vaccine (vs. joint decision with spouse) were more likely to express intent to have HPV vaccination. Perceived barriers, cues to action and self-efficacy were three of the constructs in the health belief model that significantly influenced HPV vaccination intent. A higher proportion of participants expressed willingness to pay for 2vHPV (81.2%) and 4vHPV (75.9%), as compared to 9vHPV (67.7%).

    CONCLUSION: Adults women expressed moderate intention to receive the HPV vaccine. Intervention to address barriers to uptake of the HPV vaccine among adult women in China is warranted.

  8. Lo Vecchio A, Liguoro I, Dias JA, Berkley JA, Boey C, Cohen MB, et al.
    Vaccine, 2017 03 14;35(12):1637-1644.
    PMID: 28216189 DOI: 10.1016/j.vaccine.2017.01.082
    BACKGROUND: Rotavirus (RV) is a major agent of gastroenteritis and an important cause of child death worldwide. Immunization (RVI) has been available since 2006, and the Federation of International Societies of Gastroenterology Hepatology and Nutrition (FISPGHAN) identified RVI as a top priority for the control of diarrheal illness. A FISPGHAN working group on acute diarrhea aimed at estimating the current RVI coverage worldwide and identifying barriers to implementation at local level.

    METHODS: A survey was distributed to national experts in infectious diseases and health-care authorities (March 2015-April 2016), collecting information on local recommendations, costs and perception of barriers for implementation.

    RESULTS: Forty-nine of the 79 contacted countries (62% response rate) provided a complete analyzable data. RVI was recommended in 27/49 countries (55%). Although five countries have recommended RVI since 2006, a large number (16, 33%) included RVI in a National Immunization Schedule between 2012 and 2014. The costs of vaccination are covered by the government (39%), by the GAVI Alliance (10%) or public and private insurance (8%) in some countries. However, in most cases, immunization is paid by families (43%). Elevated cost of vaccine (49%) is the main barrier for implementation of RVI. High costs of vaccination (rs=-0.39, p=0.02) and coverage of expenses by families (rs=0.5, p=0.002) significantly correlate with a lower immunization rate. Limited perception of RV illness severity by the families (47%), public-health authorities (37%) or physicians (24%) and the timing of administration (16%) are further major barriers to large- scale RVI programs.

    CONCLUSIONS: After 10years since its introduction, the implementation of RVI is still unacceptably low and should remain a major target for global public health. Barriers to implementation vary according to setting. Nevertheless, public health authorities should promote education for caregivers and health-care providers and interact with local health authorities in order to implement RVI.

  9. Loh FK, Nathan S, Chow SC, Fang CM
    Vaccine, 2019 07 09;37(30):3989-4000.
    PMID: 31186188 DOI: 10.1016/j.vaccine.2019.05.083
    Since the discovery of Toxoplasma gondii in 1908, it is estimated that one-third of the global population has been exposed to this ubiquitous intracellular protozoan. The complex life cycle of T. gondii has enabled itself to overcome stress and transmit easily within a broad host range thus achieving a high seroprevalence worldwide. To date, toxoplasmosis remains one of the most prevalent HIV-associated opportunistic central nervous system infections. This review presents a comprehensive overview of different vaccination approaches ranging from traditional inactivated whole-T. gondii vaccines to the popular DNA vaccines. Extensive discussions are made to highlight the challenges in constructing these vaccines, selecting adjuvants as well as delivery methods, immunisation approaches and developing study models. Herein we also deliberate over the latest and promising enhancement strategies that can address the limitations in developing an effective T. gondii prophylactic vaccine.
  10. 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.
  11. 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.

  12. 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: Measles-Mumps-Rubella Vaccine/administration & dosage; Measles-Mumps-Rubella Vaccine/immunology*
  13. Mariappan V, Vellasamy KM, Thimma JS, Hashim OH, Vadivelu J
    Vaccine, 2010 Feb 3;28(5):1318-24.
    PMID: 19944788 DOI: 10.1016/j.vaccine.2009.11.027
    Burkholderia cepacia is an opportunistic human pathogen associated with lung infections. Secretory proteins of B. cepacia are known to be involved in virulence and may mediate important host-pathogen interactions. In the present study, secretory proteins isolated from B. cepacia culture supernatant were separated using two-dimensional gel electrophoresis, followed by Western blot analysis to identify the immunogenic proteins. Mice antibodies raised to B. cepacia inactivated whole bacteria, outer membrane protein and culture filtrate antigen detected 74, 104 and 32 immunogenic proteins, respectively. Eighteen of these immunogenic proteins which reacted with all three antibodies were identified and might be potential molecules as a diagnostic marker or a putative candidate vaccine against B. cepacia infections.
  14. Mohammed AH, Hassan BAR, Wayyes AM, Gadhban AQ, Blebil A, Alhija SA, et al.
    Vaccine, 2022 Oct 26;40(45):6549-6557.
    PMID: 36207222 DOI: 10.1016/j.vaccine.2022.09.052
    BACKGROUND: The issue around vaccination of children has brought divergent opinions among the populations across the globe and among the Arab population. There has been a low response rate to the calls for vaccination of children and this is reflective of the sentiments which parents may have towards their children being vaccinated. This study aims to explore the parents' health beliefs, intentions, and strategies towards the COVID-19 vaccine for their children among Arab population.

    METHODS: A cross-sectional study using an online survey from October to December 2021, was carried out in five Arab countries in the Middle East. A reliable health belief model (HBM) including five domains: severity, susceptibility, benefits, barriers and cues to action, was adopted. Chi-square, Mann-Whitney test, and multivariable logistic regression were performed for data analysis.

    RESULTS: The survey response rate was 58 % (1154/2000). Only 56 % of Arab parents are intended to vaccinate their children against COVID-19. The mean scores of parental health belief are largely driven by their concern over the vaccine's side effect (p = 0.001) followed by its efficacy, safety (p 

  15. Mohd Azizi FS, Kew Y, Moy FM
    Vaccine, 2017 05 19;35(22):2955-2961.
    PMID: 28434687 DOI: 10.1016/j.vaccine.2017.04.010
    BACKGROUND: Vaccine hesitancy is a threat in combating vaccine-preventable diseases. It has been studied extensively in the Western countries but not so among Asian countries.

    OBJECTIVES: To assess the test-retest reliability of the Parent Attitudes about Childhood Vaccines (PACV) questionnaire in Malay language; to determine the prevalence of vaccine hesitancy among parents and its associations with parents' socio-demographic characteristics.

    METHODS: Forward and backward translation of PACV in Malay language was carried out. The reliability of the Malay-PACV questionnaire was tested among parents with children. The same questionnaire was used to study vaccine hesitancy among parents in a tertiary hospital in Kuala Lumpur. Information pertaining to socio-demographic characteristics, sources of information regarding vaccination and vaccine hesitancy were collected. Associations between vaccine hesitancy with socio-demographic factors were tested using Multivariable Logistic Regression.

    RESULTS: The Spearman correlation coefficient and Cronbach alpha for total PACV was 0.79 (p<0.001) and 0.79 respectively. The intra-class correlation coefficients of the subscales ranged from 0.54 to 0.90 demonstrating fair to excellent reliability. A total of 63 (11.6%) parents were noted to be vaccine hesitant. In the univariate analyses, vaccine hesitancy was associated with unemployed parents, parents who were younger, had fewer children and non-Muslim. In the multivariate model, pregnant mothers expecting their first child were four times more likely to be vaccine hesitant compared to those who already had one or more children (aOR: 3.91, 95% CI: 1.74-8.79) and unemployed parents were also more likely to be vaccine hesitant (aOR: 1.97, 95% CI: 1.08-3.59). The internet (65.6%) was the main source of information on vaccination followed by brochures (56.9%).

    CONCLUSION: The Malay-PACV questionnaire is reliable to be used. The prevalence of vaccine hesitancy among the multi-ethnic Malaysians was comparable with other populations. Pregnant mothers expecting their first child and unemployed parents were found to be more vaccine hesitant.

  16. 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.
  17. 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.
  18. Nealon J, Lim WY, Moureau A, Linus Lojikip S, Junus S, Kumar S, et al.
    Vaccine, 2019 09 16;37(39):5891-5898.
    PMID: 31445770 DOI: 10.1016/j.vaccine.2019.07.083
    BACKGROUND: The world's first dengue vaccine [Dengvaxia; Sanofi Pasteur] was licensed in 2015 and others are in development. Real-world evaluations of dengue vaccines will therefore soon be needed. We assessed feasibility of case control (CC) and test-negative (TN) design studies for dengue vaccine effectiveness by measuring associations between socio-demographic risk factors, and hospitalized dengue outcomes, in Malaysia.

    METHODS: Following ethical approval, we conducted hospital-based dengue surveillance for one year in three referral hospitals. Suspected cases aged 9-25 years underwent dengue virological confirmation by RT-PCR and/or NS1 Ag ELISA at a central laboratory. Two age- and geography-matched hospitalized non-dengue case-controls were recruited for a traditional CC study. Suspected cases testing negative were test-negative controls. Socio-demographic, risk factor and routine laboratory data were collected. Logistic regression models were used to estimate associations between confirmed dengue and risk factors.

    RESULTS: We recruited 327 subjects; 155 were suspected of dengue. The planned sample size was not met. 124 (80%) of suspected cases were dengue-confirmed; seven were assessed as severe. Three had missing RT-PCR results; the study recruited 28 test-negative controls. Only 172 matched controls could be recruited; 90 cases were matched with ≥1 controls. Characteristics of cases and controls were mostly similar. By CC design, two variables were significant risk factors for hospitalized dengue: recent household dengue contact (OR: 54, 95% CI: 7.3-397) and recent neighbourhood insecticidal fogging (OR: 2.1; 95% CI: 1.3-3.6). In the TN design, no risk factors were identified. In comparison with gold-standard diagnostics, routine tests performed poorly.

    CONCLUSIONS: The CC design may be more appropriate than the TN design for hospitalized dengue vaccine effectiveness studies. Selection bias in case control selection could be minimized by protocol changes more easily than increasing TN design control numbers, because early-stage dengue diagnosis in endemic countries is highly specific. MREC study approval: (39)KKM/NIHSEC/P16-1334.

  19. Neuhann JM, Stemler J, Carcas AJ, Frías-Iniesta J, Akova M, Bethe U, et al.
    Vaccine, 2023 Nov 22;41(48):7166-7175.
    PMID: 37919141 DOI: 10.1016/j.vaccine.2023.10.029
    BACKGROUND: Vaccination remains crucial for protection against severe SARS-CoV-2 infection, especially for people of advanced age, however, optimal dosing regimens are as yet lacking.

    METHODS: EU-COVAT-1-AGED Part A is a randomised controlled, adaptive, multicentre phase II trial evaluating safety and immunogenicity of a 3rd vaccination (1st booster) in individuals ≥75 years. Fifty-three participants were randomised to full-doses of either mRNA-1273 (Spikevax®, 100 µg) or BNT162b2 (Comirnaty®, 30 µg). The primary endpoint was the rate of 2-fold circulating antibody titre increase 14 days post-vaccination measured by quantitative electrochemiluminescence (ECL) immunoassay, targeting RBD region of Wuhan wild-type SARS-CoV-2. Secondary endpoints included the changes in neutralising capacity against wild-type and 25 variants of concern at 14 days and up to 12 months. Safety was assessed by monitoring of solicited adverse events (AEs) for seven days after on-study vaccination. Unsolicited AEs were collected until the end of follow-up at 12 months, SAEs were pursued for a further 30 days.

    RESULTS: Between 08th of November 2021 and 04th of January 2022, 53 participants ≥75 years received a COVID-19 vaccine as 1st booster. Fifty subjects (BNT162b2 n = 25/mRNA-1273 n = 25) were included in the analyses for immunogenicity at day 14. The primary endpoint of a 2-fold anti-RBD IgG titre increase 14 days after vaccination was reached for all subjects. A 3rd vaccination of full-dose mRNA-1273 provided higher anti-RBD IgG titres (Geometric mean titre) D14 mRNA-127310711 IU/mL (95 %-CI: 8003;14336) vs. BNT162b2: 7090 IU/mL (95 %-CI: 5688;8837). We detected a pattern showing higher neutralising capacity of full-dose mRNA-1273 against wild-type as well as for 23 out of 25 tested variants.

    INTERPRETATION: Third doses of either BNT162b2 or mRNA-1273 provide substantial circulating antibody increase 14 days after vaccination. Full-dose mRNA-1273 provides higher antibody levels with an overall similar safety profile for people ≥75 years.

    FUNDING: This trial was funded by the European Commission (Framework Program HORIZON 2020).

    Matched MeSH terms: Immunogenicity, Vaccine
  20. Ng SS, Hutubessy R, Chaiyakunapruk N
    Vaccine, 2018 05 03;36(19):2529-2544.
    PMID: 29625764 DOI: 10.1016/j.vaccine.2018.03.024
    BACKGROUND: The success of human papillomavirus (HPV) national immunization program depends on effective strategies in optimizing the uptake of HPV vaccine. Given the increasing number of economic evaluations, this review was conducted to update the economic evidence on HPV vaccination, by focusing on: (i) 9-valent vaccine compared to bi- or quadrivalent vaccine; (ii) gender-neutral vaccination compared to female only vaccination; and (iii) multiple age cohort immunization compared to single age cohort immunization.

    METHODS: Searches were performed until June 2016 using 4 databases: PubMed; Embase; Cochrane Library; and LILACS. The combined WHO, Drummond and CHEERS checklist were used to evaluate the quality of included studies.

    RESULTS: Thirty-four studies were included in the review and most of them were conducted in high-income countries. The inclusion of adolescent boys in vaccination program was found to be cost-effective if vaccine price and coverage was low. When coverage for female was above 75%, gender-neutral vaccination was less cost-effective than when targeting only girls aged 9-18 years. Current evidence does not show conclusive proof of greater cost-effectiveness of 9-valent vaccine compared to the older HPV vaccines as the price for 9-valent vaccine was still uncertain. Multicohort immunization strategy was cost-effective in the age range 9-14 years but the upper age limit at which vaccination was no longer cost-effective needs to be further investigated. Key influential parameters identified were duration of vaccine protection, vaccine price, coverage, and discounting rates.

    CONCLUSIONS: These findings are expected to support policy-makers in making recommendations for HPV immunization programs on either switching to the 9-valent vaccine or inclusion of adolescent boys' vaccination or extending the age of vaccination.

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