Safety and immunogenicity of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy Thai adults aged 18-64 years in Nakhon Phanom: A Phase III double blinded, three-arm, randomized, controlled trial.

BACKGROUND: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. METHODS: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. RESULTS: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = -22.0-76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: -2.77, 6.25), 2.22 (-2.40, 6.84), and -0.57 (-5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) CONCLUSIONS: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.

Seroprevalence of anti-SARS-CoV-2 antibodies and associated factors among household contacts of COVID-19 confirmed cases in Bangkok, Thailand.

Background: High COVID-19 transmission among household (HH) contacts of infected cases were reported with seroprevalence varying from 5.5% to 57.2% worldwide. Data on seroprevalence among HH contacts and factors associated with seropositivity in Thailand are limited. Objectives: To determine the seroprevalence and factors associated with anti-SARS-CoV-2 antibodies among HH contacts of COVID-19 confirmed cases. Materials and methods: Data on confirmed COVID-19 cases (primary cases) in Bangkok from March 2020-July 2021 were retrieved from Institute for Urban Disease Control and Prevention. Primary cases were contacted within 14 days of testing positive for permission to contact their HH contacts via telephone. HH contacts were then recruited to complete questionnaires about demographics, and risk factors and blood was collected and tested for total immunoglobulin antibody against SARS-CoV-2 spike S1 protein. Factors associated with seropositivity were analysed by logistic regression. Results: Eligible participants of 452 HH contacts of infected cases in Bangkok were contacted. Seroprevalence was 20.5% among HH contacts. Factors associated with seropositivity after multivariate analysis were relationship to index case (being other relatives to index case (other than close relatives/spouse) [aOR 4.04, 95% CI; 1.15, 14.14, p.029] and being a co-worker to index cases [aOR 0.16, 95% CI; 0.045, 0.60, p.006]), always staying in the same room with index case [aOR 5.64, 95% CI; 1.95, 16.34, p.001], sharing utensil [aOR 0.25, 95% CI; 0.074, 0.82, p.023], and participation in leisure activities together with index case [aOR 4.77, 95% CI; 1.47, 15.51, p.009]. Conclusion: Serological investigation can be used in detecting COVID-19 infection in conjunction with other molecular techniques. It is a useful tool for studies on seroprevalence in a population as well as seroconversion after a vaccination campaign. Sharing living environments are associated with seropositivity in HH contacts. Nevertheless, individual practices can be affected by awareness, cultural differences, and control measures implemented by each country.

Antibody responses induced by trivalent inactivated influenza vaccine among pregnant and non-pregnant women in Thailand: A matched cohort study.

BACKGROUND: We compared influenza antibody titers among vaccinated and unvaccinated pregnant and non-pregnant women. METHODS: During 1st June- 30th September 2018, four groups of cohort participants-vaccinated pregnant, unvaccinated pregnant, vaccinated non-pregnant, and unvaccinated non-pregnant women were selected by matching age, gestational age, and the week of vaccination. Serum antibody titers against each strain of 2018 Southern Hemisphere inactivated trivalent influenza vaccine (IIV3) were assessed by hemagglutination inhibition (HI) assay on Day 0 (pre-vaccination) and Day 28 (one month post-vaccination) serum samples. Geometric mean titer (GMT), GMT ratio (GMR), seroconversion (defined as ≥4 fold increase in HI titer), and seroprotection (i.e. HI titer ≥1:40) were compared across the study groups using multilevel regression analyses, controlling for previous year vaccination from medical records and baseline antibody levels. RESULTS: A total of 132 participants were enrolled in the study (33 in each of the four study groups). The baseline GMTs for influenza A(H1N1), A(H3N2), and B vaccine strains were not significantly different among all four groups (all p-values >0.05). After one month, both vaccinated groups had significantly higher GMT, GMR, seroconversion, and seroprotection than their unvaccinated controls (all p-values <0.05). The seroconversion rate was over 60% for any strain among the vaccinated groups, with the highest (88.8%) observed against A(H1N1) in the vaccinated pregnant group. Similarly, at least 75% of the vaccinated participants developed seroprotective antibody levels against all three strains; the highest seroprotection was found against A(H3N2) at 92.6% among vaccinated non-pregnant participants. Antibody responses (post-vaccination GMT, GMR, seroconversion, and seroprotection) were not significantly different between pregnant and non-pregnant women for all three strains of IIV3 (all p>0.05). CONCLUSIONS: The 2018 seasonal IIV3 was immunogenic against all three vaccine strains and pregnancy did not seem to alter the immune response to IIV3. These findings support the current influenza vaccination recommendations for pregnant women.

Underlying cardiopulmonary conditions as a risk factor for influenza and respiratory syncytial virus infection among community-dwelling adults aged ≥ 65 years in Thailand: Findings from a two-year prospective cohort study.

BACKGROUND: Adults with cardiopulmonary conditions may be at increased risk of influenza and respiratory syncytial virus (RSV) infection, but it is not well-established and few data are available from middle-income countries. METHODS: Using data from a prospective cohort study of influenza vaccine effectiveness, we estimated and compared the incidences of influenza and RSV between community-dwelling Thai adults aged ≥ 65 years with and without cardiopulmonary conditions. During May 2015-May 2017, older adults in a rural province in Thailand were followed-up with weekly surveillance for acute respiratory illness (ARI), defined broadly as new onset or worsening of cough with or without fever, and hospitalized ARI. When ill, nasal self-swabs and/or nasopharyngeal swabs were collected for reverse-transcription polymerase chain reaction testing. We used Poisson regression to calculate incidence rate ratios (IRR), adjusting for age, sex, current smoking, number of hospital visits, weekly influenza activity, and influenza vaccination. RESULTS: Overall, 3220 adults with a median age of 71 years (IQR 68-76) were enrolled; 1324 (41.1%) were male; and 313 (9.7%) had ≥1 underlying cardiopulmonary condition, most commonly chronic obstructive pulmonary disease (131; 41.2%) or asthma (73; 23.3%). Participants with cardiopulmonary conditions had higher incidences of ARI, influenza, and RSV than those without (Adjusted IRR: 1.84, 95% CI 1.64-2.07; 1.86, 95% CI 1.07-3.26; 2.04, 95% CI 1.11-3.76, respectively). CONCLUSION: Older adults in rural Thailand with cardiopulmonary conditions have increased rates of ARI, influenza, and RSV infections. Our findings support efforts to ensure this population has access to influenza vaccines and other respiratory illness prevention measures.