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Immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates

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.
Changes in the prevalence of influenza-like illness and influenza vaccine uptake among Hajj pilgrims: A 10-year retrospective analysis of data

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.
Hepatitis A shifting epidemiology in South-East Asia and China

Barzaga BN

Vaccine, 2000 Feb 18;18 Suppl 1:S61-4.
PMID: 10683551

A review of the epidemiology of hepatitis A virus (HAV) infection over the last 20 years shows shifting patterns in the prevalence of antibodies to HAV (anti-HAV) throughout South-East Asia and China. A number of countries have shifted from high to moderate and from moderate to low endemicity, with a corresponding increase in the age of exposure from childhood to early adulthood. The changes have resulted from improvements in hygiene, sanitation and the quality of drinking water, reflecting improvements in living standards and socioeconomic progress. In general in the late 1970s and early 1980s, 85-95% of the population of developing countries like the Philippines, Korea, China and Thailand were anti-HAV-positive by age 10-15 years, compared with only about 50% in the more affluent countries like Malaysia and Singapore. In the early 1990s, 85-95% of the population were immune by age 30-40 years in the Philippines, Korea, China and Thailand, and by 50 years of age and above in Malaysia and Singapore. Similar trends were noted in Hong Kong, Taiwan and Japan. Exposure to HAV at a later age may be associated with an increase in hepatitis A morbidity and a greater propensity for outbreaks.
Epidemiological data on pneumococcal infections in Asian countries

Jamal F

Vaccine, 1999 Jul 30;17 Suppl 1:S75-8.
PMID: 10471186
Hepatitis B epidemiology in Asia, the Middle East and Africa

André F

Vaccine, 2000 Feb 18;18 Suppl 1:S20-2.
PMID: 10683538

Asia and Africa have previously been classified as areas of high endemicity for hepatitis B virus (HBV), but in some countries highly effective vaccination programmes have shifted this pattern towards intermediate or low endemicity. Thus, China is now the only country in Asia where HBV endemicity is high. Countries with intermediate endemicity include India, Korea, the Philippines, Taiwan and Thailand, and those with low endemicity include Japan, Pakistan, Bangladesh, Singapore, Sri Lanka and Malaysia. Most countries in Africa have high HBV endemicity, with the exceptions of Tunisia and Morocco, which have intermediate endemicity. Zambia has borderline intermediate/high endemicity. In the Middle East, Bahrain, Iran, Israel and Kuwait are areas of low endemicity, Cyprus, Iraq and the United Arab Emirates have intermediate endemicity, and Egypt, Jordan, Oman, Palestine, Yemen and Saudi Arabia have high endemicity. All of these Middle East countries reach a large proportion of their population with hepatitis B vaccination, which is reducing the infection rate, particularly in Saudi Arabia. The vaccination programme in Taiwan has also greatly reduced the HBV infection rate. Future vaccination programmes must take into account the mode of transmission of HBV, the healthcare infrastructure to deliver vaccination, and the socioeconomic and political factors in each individual country, to determine the most cost-effective way of infection control.
Immunization coverage required to prevent outbreaks of dog rabies

Coleman PG, Dye C

Vaccine, 1996 Feb;14(3):185-6.
PMID: 8920697

WHO recommends that 70% of dogs in a population should be immunized to eliminate or prevent outbreaks of rabies. This critical percentage (pc) has been established empirically from observations on the relationship between vaccination coverage and rabies incidence in dog populations around the world. Here, by contrast, we estimate pc by using epidemic theory, together with data available from four outbreaks in urban and rural areas of the USA, Mexico, Malaysia and Indonesia. From the rate of increase of cases at the beginning of these epidemics, we obtain estimates of the basic case reproduction number of infection, R0, in the range 1.62-2.33, implying that pc lies between 39% and 57%. The errors attached to these estimates of pc suggest that the recommended coverage of 70% would prevent a major outbreak of rabies on no fewer than 96.5% of occasions.
Fulltext Cost-effectiveness of dengue vaccination in ten endemic countries

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.
Fulltext Feasibility of case-control and test-negative designs to evaluate dengue vaccine effectiveness in Malaysia

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.
Repeated dose toxicity evaluation of a cold chain-free, live, attenuated oral cholera vaccine in Sprague Dawley rats

Xian TH, Parasuraman S, Sinniah K, Ravichandran M, Prabhakaran G

Vaccine, 2019 01 29;37(5):711-720.
PMID: 30630696 DOI: 10.1016/j.vaccine.2018.12.027

The repeated dose toxicity of a prototype cold chain-free, live, attenuated oral cholera vaccine containing 5 × 106 CFU/mL of the VCUSM14P strain was evaluated in Sprague Dawley (SD) rats (single dose administered daily for 30 days) to ascertain its safety for clinical use. Repeated dose toxicity studies for cholera vaccines in the literature have administered 2 or 3 fixed doses at 7, 14, 21 or 69 day intervals. The present study reports an evaluation of 30 repeated doses of cholera vaccine administered at three different concentrations (Group II (1.25 × 106 CFU), Group III (2.5 × 106 CFU) and Group IV (5 × 106 CFU)) in SD rats. The liquid vaccine was administered orally to the rats with the respective dose every day, and normal saline was administered to the control group (Group I). No significant difference (P > 0.05) was observed in the body weights and biochemical parameters of the rats after 15 and 30 repeated doses compared to those of the control group. However, compared to those of Group I, a significant increase (P 
Factors influencing intention to obtain the HPV vaccine and acceptability of 2-, 4- and 9-valent HPV vaccines: A study of undergraduate female health sciences students in Fujian, China

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.
Monitoring human papillomavirus prevalence among young Australian women undergoing routine chlamydia screening

Shilling H, Murray G, Brotherton JML, Hawkes D, Saville M, Sivertsen T, et al.

Vaccine, 2020 01 29;38(5):1186-1193.
PMID: 31767467 DOI: 10.1016/j.vaccine.2019.11.019

INTRODUCTION: Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women.
METHODS: De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay.
RESULTS: Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women.
CONCLUSIONS: HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.
Vaccine hesitancy towards childhood immunisation amongst urban pregnant mothers in Malaysia

Kalok A, Loh SYE, Chew KT, Abdul Aziz NH, Shah SA, Ahmad S, et al.

Vaccine, 2020 02 24;38(9):2183-2189.
PMID: 32001070 DOI: 10.1016/j.vaccine.2020.01.043

BACKGROUND: Vaccine hesitancy is a complex behaviour which involves various degrees of indecision about specific vaccines or vaccination uptake. Access to antenatal care had been associated with positive vaccine behavior.
OBJECTIVE: To determine the prevalence of vaccine hesitancy towards childhood immunisation amongst urban pregnant mothers and the associated socio-demographic factors.
METHODS: A cross-sectional study was conducted among 1081 women who received antenatal care at a teaching hospital in Kuala Lumpur. Vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines (PACV) Survey in both English and validated Malay versions. The sociodemographic data of the mothers and their partners, source of vaccine information and reasons for hesitancy were analysed.
RESULTS: Eighty-six (8.0%) pregnant mothers were vaccine hesitant. Ethnicity, religion, number of children, educational level and employment status were significantly associated with vaccine hesitancy. Multivariable analysis showed that a low level of education was the most significant risk factor (p
Fulltext Cholera in selected countries in Asia

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.
Cross-protective efficacy of the O1 Manisa + O 3039 bivalent vaccine and the O 3039 monovalent vaccine against heterologous challenge with FMDV O/Jincheon/SKR/2014 in pig

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.
Changes in serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from adult patients in Asia: Emergence of drug-resistant non-vaccine serotypes

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.
Carriage of Haemophilus influenzae among children attending childcare centres in Kuala Lumpur, Malaysia in the post vaccination era: A cross-sectional study

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 
Acceptance and willingness to pay for a hypothetical vaccine against monkeypox viral infection among frontline physicians: A cross-sectional study in Indonesia

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.
Fulltext Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen

Nyon MP, Du L, Tseng CK, Seid CA, Pollet J, Naceanceno KS, et al.

Vaccine, 2018 03 27;36(14):1853-1862.
PMID: 29496347 DOI: 10.1016/j.vaccine.2018.02.065

Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.

Matched MeSH terms: Immunogenicity, Vaccine
Establishment of Asia-Pacific Network for Enterovirus Surveillance

Chiu ML, Luo ST, Chen YY, Chung WY, Duong V, Dussart P, et al.

Vaccine, 2020 01 03;38(1):1-9.
PMID: 31679864 DOI: 10.1016/j.vaccine.2019.09.111

Enteroviruses (EV), the major pathogens of hand, foot, and mouth disease (HFMD) and herpangina, affect millions of children each year. Most human enteroviruses cause self-limited infections except polioviruses, enterovirus A71 (EV-A71), enterovirus D68 (EV-D68), and several echoviruses (Echo) and coxsackieviruses (CV). Especially, EV-A71 has repeatedly caused large-scale outbreaks in the Asia-Pacific region since 1997. Some Asian countries have experienced cyclical outbreaks of severe EV-A71 infections and initiated development of EV-A71 vaccines. Five EV-A71 vaccine candidates have been clinically evaluated and three of them were approved for marketing in China. However, none of the China-approved products seek marketing approval in other countries. This situation supports a role for collaboration among Asian countries to facilitate clinical trials and licensure of EV-A71 vaccines. Additionally, enterovirus D68 outbreaks have been reported in the US and Taiwan currently and caused severe complications and deaths. Hence, an Asia-Pacific Network for Enterovirus Surveillance (APNES) has been established to estimate disease burden, understand virus evolution, and facilitate vaccine development through harmonizing laboratory diagnosis and data collection. Founded in 2017, the APNES is comprised of internationally recognized experts in the field of enterovirus in Asian countries working to raise awareness of this potentially fatal and debilitating disease. This article demonstrated the summaries of the first expert meeting, 2017 International Workshop on Enterovirus Surveillance and Vaccine Development, held by APNES in Taipei, Taiwan, March 2017.
Vaccine candidates generated by codon and codon pair deoptimization of enterovirus A71 protect against lethal challenge in mice

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.

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