Immune responses of the third dose of AZD1222 vaccine or BNT162b2 mRNA vaccine after two doses of CoronaVac vaccines against Delta and Omicron variants

SummaryHalf-dose AZD1222 or BNT162b2 boosters maintained immunogenicity and safety, and were non-inferior to full doses. All doses elicited high immunogenicity and best with extended post-CoronaVac primary-series intervals (120-180 days) and high-transmissibility Omicron. MethodsAt 60-to-<90, 90-to-<120, or 120-to-180 days ( intervals) post-CoronaVac primary-series, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, and followed up at day-28, -60 and -90. Vaccination-induced immunogenicity to Ancestral, Delta and Omicron BA.1 strains were evaluated by assessing anti-spike ( anti-S), anti-nucleocapsid antibodies, pseudovirus neutralization ( PVNT), micro-neutralization titers, and T-cells assays. Descriptive statistics and non-inferiority cut-offs were reported as geometric mean concentration (GMC) or titer (GMT) and GMC/GMT ratios comparing baseline to day-28 and day-90 seroresponses, and different intervals post-CoronaVac primary-series. Omicron immunogenicity was only evaluated in full-dose recipients. FindingsNo serious or severe vaccine-related safety events occurred. All assays and intervals showed non-inferior immunogenicity between full-doses and half-doses. However, full-dose vaccines and/or longer, 120-to-180-day intervals substantially improved immunogenicity (in GMC measured by anti-S assays or GMT measured by PVNT50; p <0.001). Within platforms and regardless of dose or platform, seroconversions were over 97%, and over 90% for pseudovirus neutralizing antibodies, but similar against the SARS-CoV-2 strains. Immunogenicity waned more quickly with half-doses than full-doses between day 60-to-90 follow-ups, but remained high against Ancestral or Delta strains. Against Omicron, the day-28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines. InterpretationCombining heterologous schedules, fractional dosing, and extended post-second dose intervals, broadens population-level protection and prevents disruptions, especially in resource-limited settings. FundingFunding was provided by the Program Management Unit for Competitiveness Enhancement (PMU-C) National research, National Higher Education, Science, Research and Innovation Policy Council, Thailand through Clinixir Ltd. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSO_LIAlthough nAb titers from CoronaVac primary series waned after 3-4 months, nAb were more increased when boosted at 8 months than at 2 months post-primary series. C_LIO_LISix months post-vaccination with a one-fourth dose of primary mRNA-1273, nAb responses were half as robust as full doses, but VE was over 80% of that of full-dose vaccinations. C_LIO_LIThai adults boosted with 30g-BNT162b2 and 15g-BNT162b2 at 8-12 weeks after two-dose CoronaVac or AZD1222 had high antibodies to the virus receptor-binding domain, nAb titers against all variants, and T-cell responses. C_LIO_LIThird-dose boosting at a 44-45-week interval significantly increased antibody levels compared to boosting at 15-25-week or 8-12-week intervals. C_LIO_LIA third dose of CoronaVac administered eight months after the second dose increased antibody levels more than when administered at two months, while antibody responses were two-fold higher with a booster dose of AZD1222 administered at a 12-weeks or longer interval than a 6-weeks or shorter interval.Error! Bookmark not defined. C_LIO_LIIn the UK, third doses of AZD1222 led to higher antibody levels that correlated with high efficacy and T-cell responses, after a prolonged, dose-stretched interval between vaccine doses, than shorter intervals. C_LIO_LIOmicron-neutralizing antibodies were detected in only 56% of short-interval vaccine recipients versus all (100%) prolonged-interval vaccine recipients, 69% of whom also demonstrated Omicron-neutralizing antibodies at 4-6 months post-booster. C_LIO_LIIsraeli studies noted a restoration of antibody levels and enhanced immunogenic protection against severe disease when a second booster (fourth dose) was given 4 months or longer after a first booster, with no new safety concerns. C_LI Added value of this studyThere were no studies designed specifically aimed to analyzed non inferiority between the full dose and half dose of AZD1222 or BNT162b2 boosters after CoronaVac two doses which is important research question when we started the study and the situation of limited vaccine supply, global inequity and high disease burden in the Lower middle-income countries Data on the optimal prime-boost interval is limited, especially data that combines lower (fractional) dosing from resource-limited countries, which is provided by our study. Implications of all the available evidenceWe confirm the feasibility of a booster strategy that accounts for the needs of resource-limitations, through the use of fractional dosing, dose-stretching and heterologous schedules, which can broaden population-level protection and prevent vaccination disruptions.

Safety and Immunogenicity of An Egg-Based Inactivated Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomized, Placebo-Controlled, Phase 1/2 Trial in Vietnam

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus (NDV) vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1. The spike protein was stabilized and incorporated into NDV virions by removing the polybasic furin cleavage site, introducing the transmembrane domain and cytoplasmic tail of the fusion protein of NDV, and introducing six prolines for stabilization in the prefusion state. Vaccine production and clinical development was initiated in Vietnam, Thailand, and Brazil. Here the interim results from the first stage of the randomized, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial conducted at the Hanoi Medical University (Vietnam) are presented. Healthy adults aged 18-59 years, non-pregnant, and with self-reported negative history for SARS-CoV-2 infection were eligible. Participants were randomized to receive one of five treatments by intramuscular injection twice, 28 days apart: 1 g +/-CpG1018 (a toll-like receptor 9 agonist), 3 g alone, 10 g alone, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited adverse events (AEs) during 7 days and subject-reported AEs during 28 days after each vaccination. Investigators further reviewed subject-reported AEs. Secondary outcomes were immunogenicity measures (anti-spike immunoglobulin G [IgG] and pseudotyped virus neutralization). This interim analysis assessed safety 56 days after first vaccination (day 57) in treatment-exposed individuals and immunogenicity through 14 days after second vaccination (day 43) per protocol. Between March 15 and April 23, 2021, 224 individuals were screened and 120 were enrolled (25 per group for active vaccination and 20 for placebo). All subjects received two doses. The most common solicited AEs among those receiving active vaccine or placebo were all predominantly mild and included injection site pain or tenderness (<58%), fatigue or malaise (<22%), headache (<21%), and myalgia (<14%). No higher proportion of the solicited AEs were observed for any group of active vaccine. The proportion reporting vaccine-related AEs during the 28 days after either vaccination ranged from 4% to 8% among vaccine groups and was 5% in controls. No vaccine-related serious adverse event occurred. The immune response in the 10 g formulation group was highest, followed by 1 g +CpG1018, 3 g, and 1 g formulations. Fourteen days after the second vaccination, the geometric mean concentrations (GMC) of 50% neutralizing antibody against the homologous Wuhan-Hu-1 pseudovirus ranged from 56.07 IU/mL (1 g, 95% CI 37.01, 84.94) to 246.19 IU/mL (10 g, 95% CI 151.97, 398.82), with 84% to 96% of vaccine groups attaining a [≥] 4-fold increase over baseline. This was compared to a panel of human convalescent sera (N=29, 72.93 95% CI 33.00-161.14). Live virus neutralization to the B.1.617.2 (Delta) variant of concern was reduced but in line with observations for vaccines currently in use. Since the adjuvant has shown modest benefit, GMC ratio of 2.56 (95% CI, 1.4 - 4.6) for 1 g +/-CpG1018, a decision was made not to continue studying it with this vaccine. NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 g dose was advanced to phase 2 along with a 6 g dose. The 10 g dose was not selected for evaluation in phase 2 due to potential impact on manufacturing capacity. ClinicalTrials.gov NCT04830800.

Safety and Immunogenicity of an Inactivated Recombinant Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomised, Placebo-Controlled, Phase 1/2 Trial

BackgroundProduction of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. MethodsThis phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 {micro}g{+/-}CpG1018 (a toll-like receptor 9 agonist), 3 {micro}g{+/-}CpG1018, 10 {micro}g, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). FindingsBetween March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5{middle dot}7% to 17{middle dot}1% among vaccine groups and was 2{middle dot}9% in controls; there was no vaccine-related serious adverse event. The 10 {micro}g formulations immunogenicity ranked best, followed by 3 {micro}g+CpG1018, 3 {micro}g, 1 {micro}g+CpG1018, and 1 {micro}g formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122{middle dot}23 IU/mL (1 {micro}g, 95% CI 86{middle dot}40-172{middle dot}91) to 474{middle dot}35 IU/mL (10 {micro}g, 95% CI 320{middle dot}90-701{middle dot}19), with 93{middle dot}9% to 100% of vaccine groups attaining a [≥]4-fold increase over baseline. InterpretationNDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 {micro}g and 3 {micro}g+CpG1018 formulations advanced to phase 2. FundingNational Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA)

User Acceptance of Electronic Medical Record System: Implementation at Marie Stopes International, Myanmar / 대한의료정보학회지

Objectives@#This study assessed the technical feasibility and aimed to determine the factors influencing intention to use Electronic Medical Records (EMRs) at Marie Stopes International, Myanmar (MSI-M). @*Methods@#A cross-sectional survey was conducted among 112 participants who were working at the clinics and head office of MSI-M. Demographic information, type of office, technical feasibility, information communication technology knowledge, computer usage, and user acceptance towards the proposed system were obtained from the participants. @*Results@#The results indicated low health information technology usage and network availability at MSI-M clinics. Positive perception of EMRs was found among the staff members of MSI-M, which was reflected by positive responses regarding perceived usefulness (average score of 4.15), perceived ease of use (average score of 4.03), and intention to use (average score of 4.10) on a 5-point Likert scale. Statistically, staff from the head office expressed less desire to implement an EMR system (odds ratio = 0.07; 95% confidence interval, 0.01–0.97), especially when they do not perceive the usefulness of the system (odds ratio = 5.05; 95% confidence interval, 2.39–10.69). @*Conclusions@#Since health information technology usage and network availability were low in MSI-M, it is important to strengthen the information and communication technology infrastructure and introduce a policy for capacity building at MSI-M. Adequate training and strong leadership support are recommended for the successful initial implementation and sustainability of an EMR system at MSI-M.

Prevalence and Alternative Treatment of Head-Lice Infestation in Rural Thailand: A Community-Based Study

Head-lice infestation, pediculosis capitis, remains a public-health burden in many countries. The widely used first-line pediculicides and alternative treatments are often too costly for use in poor socio-economic settings. Ivermectin has been considered an alternate treatment for field practice. This study was composed of 2 parts, a cross-sectional survey and an intervention study. The main objectives were to determine the prevalence and potential factors associated with head-lice infestation, and to evaluate the effectiveness and safety of oral ivermectin administration. A community-based cross-sectional survey was conducted among 890 villagers in rural areas along Thai-Myanmar border. Females with infestations were eligible for the intervention study, and 181 participated in the intervention study. A post-treatment survey was conducted to assess acceptance of ivermectin as a treatment choice. Data analysis used descriptive statistics and a generalized-estimation-equation model adjusted for cluster effect. The study revealed the prevalence of head-lice infestation was 50% among females and only 3% among males. Age stratification showed a high prevalence among females aged <20 years, and among 50% of female school-children. The prevalence was persistent among those with a history of infestation. The major risk factors were residing in a setting with other infected cases, and sharing a hair comb. The study also confirmed that ivermectin was safe and effective for field-based practice. It was considered a preferable treatment option. In conclusion, behavior-change communication should be implemented to reduce the observed high prevalence of head-lice infestation. Ivermectin may be an alternative choice for head-lice treatment, especially in remote areas.

Addressing challenges faced by insecticide spraying for the control of dengue fever in Bangkok, Thailand: a qualitative approach.

Background: This study focused on evaluating the fumigation scheme and identifying problems encountered during the operation in the Bangkok Metropolitan Administration area. Methods: Ten district health officers working in different fumigation teams of the dengue outbreak control programme around Bangkok had participated in an in-depth interview. Five predetermined themes, including (i) dengue surveillance and control strategy, (ii) quality and availability of equipment, (iii) delays, (iv) human resources, and (v) area coverage, and other emerging themes were addressed during the interviews. Results: Although the staff seemed to know the operation protocol of the dengue surveillance and control programmes well, they encountered some difficulties in accessing households for proper spraying, and a lack of human and material resources, especially during an outbreak. Other emerging themes concerned inefficient communications among the sectors from hospital to district offices, leading to inaccurate or missing patient addresses for spraying, and the lack of community networks and public cooperation for the dengue control programmes. Conclusions: The findings suggest that coordination among the relevant health sectors to acquire accurate and timely information about dengue cases is essential. Involving community networks should help to improve public engagement with and participation in the surveillance and outbreak control programmes.