Immunogenicity and safety in healthy adults of full dose versus half doses of COVID-19 vaccine (ChAdOx1-S or BNT162b2) or full-dose CoronaVac administered as a booster dose after priming with CoronaVac: a randomised, observer-masked, controlled trial in Indonesia.

BACKGROUND: Inactivated COVID-19 vaccines effectively prevent death, but their effectiveness for preventing infection or severe illness is known to decrease within 3-6 months following the second priming dose. Here we aimed to evaluate the immunogenicity and safety of three potential booster vaccines administered as a full-dose homologous booster or full-dose or half-dose heterologous boosters among individuals primed with CoronaVac. METHODS: We did an observer and participant masked, randomised controlled trial study of healthy Indonesian adults from five recruitment sites in Bandung and Jakarta, Indonesia, aged 18 years and older who had previously received two doses of CoronaVac within 3 to less than 6 months or 6 to 9 months before the booster dose. Participants were randomly assigned (1:1:1:1:1) by means of stratified randomisation with random block size to a homologous booster with full-dose CoronaVac or heterologous boosters with ChAdOx1-S or BNT162b2 in full dose or half dose. The primary outcome was to evaluate the seropositive, seroconversion rate, and the geometric mean titres of IgG anti-spike-receptor binding domain and neutralising antibodies, 28 days after booster dose vaccination in the per-protocol population. Safety was assessed as a secondary outcome in all vaccinated booster participants by the incidence rate and intensity of adverse events within 24 h, 7 days, and 28 days after the booster dose. This study is registered with ina-registry.org, INA-GO0HLGB, and is complete. FINDINGS: Between Nov 26 and Dec 16, 2021, 1015 people were screened, and 960 healthy adults were enrolled; 190-193 were included in each group. 28 days after receiving the booster, combining the 3 to less than 6 months and 6 to 9 months groups, the proportions of seroconversion rates in each vaccine group were ChAdOx1-S 75 (82%) of 92 to 87 (88%) of 99 for full dose and half dose, BNT162b2 92 (92%) of 100 to 90 (98%) of 92 for full dose and half dose, and CoronaVac in 38 (41%) of 92 to 65 (66%) of 98. All booster groups achieved 100% seropositivity 28 days after the booster dose. Participants in the 6 to 9 months priming group achieved higher titres compared with participants in the 3 to less than 6 months priming group. The geometric mean titres in participants in the 6 to 9 months priming group in each vaccine group were ChAdOx1-S 11258·69 (9562·43-13 255·85) and 7853·04 (6698·92-9206·00) for full dose and half dose, BNT162b2 19999·84 (17 720·58-22 572·25) and 17 017·62 (14 694·40-19 708·16) for full dose and half dose and CoronaVac 1440·55 (1172·81-1769·42) achieved higher titres compared with participants in the 3 to less than 6 months priming group which in each vaccine group were ChAdOx1-S 7730·39 (6401·87-9334·60) and 6684·34 (5678·94-7867·73) for full dose and half dose, BNT162b2 16594·08 (13 993·08-19 678·55) and 12 121·67 (9925·21-14 804·19) for full dose and half dose, and CoronaVac 1210·23 (976·49-1499·92). The median percentage inhibition for the surrogate virus neutralisation test against the delta B.1.617.2 and wild-type (WT) variant before the booster and 28 days after the booster dose was very high in all groups (p<0·001), all with greater than 90% inhibition against both delta and WT strains. No serious adverse events were associated with the vaccines. Within the heterologous booster groups, the adverse event rates in the half-dose groups were lower compared with the full-dose groups. INTERPRETATION: Geometric mean titre values between participants in the 6 to 9 months priming group and the 3 to less than 6 months priming group before the booster dose and between half-dose and full-dose groups 28 days before the booster were not significantly different for half-dose ChAdOx1-S, full-dose BNT162b2, and CoronaVac and were significantly different for full-dose ChAdOx1-S and half-dose BNT162b2. Among individuals primed with CoronaVac, boosting with BNT162b2 (full dose or half dose) or ChAdOx1-S (full dose or half dose) produces substantially better immune responses than in those boosted with CoronaVac. Full-dose and half-dose boosting with either BNT162b2 or ChAdOx1-S produced similar responses. Heterologous booster with half-dose might be considered in adults primed with two doses of CoronaVac vaccine. FUNDING: Ministry of Health, Indonesia. TRANSLATION: For the Indonesian translation of the abstract see Supplementary Materials section.

Plasma retinol level, vitamin A supplementation and acute respiratory infections in children of 1-5 years old in a developing country. Respiratory Diseases Working Group.

STUDY OBJECTIVE: To evaluate the relationship between vitamin A supplementation, plasma retinol level (PRL) and incidence, severity and duration of acute respiratory infect ions (ARI) in children 1-5 years old. DESIGN AND SETTING: A one year prospective randomized intervention study from June 1989 to May 1990 in Cikutra, a suburb of Bandung, Indonesia. SUBJECTS AND MEASUREMENTS: Out of almost 2000 children aged 12-54 months, 269 were selected by stratified randomization. Vitamin A (200,000 IU orally) was administered at 6-monthly intervals in a double blind, placebo controlled programme. Every 2 weeks, primary health care workers collected data on respiratory symptoms in the children, and every month a pediatrician examined the children. Venous blood samples were obtained at the start and at 3 and 6 months for plasma retinol levels (PRL). RESULTS: The mean PRL at the start of the study was 20 +/- 8 micrograms/dl; 8% of the children showed a deficient level of less than 10 micrograms/dl. The incidence or ARI was 6.7 +/- 3.5 episodes per child per year with a mean duration of 5.3 +/- 3.1 days per episode. In vitamin A supplemented children the duration of ARI was slightly shorter (5.2 +/- 3.1 versus 5.6 +/- 3.1 days, P < 0.01) but no effect on the incidence or severity of ARI was detected. Low, and especially deficient, PRL had improved after 3 months and even after 6 months, but this was unrelated to vitamin A supplementation. There was also no relationship between PRL and incidence, severity or duration of ARI. CONCLUSIONS: Only a slight relationship is found between vitamin A supplementation and ARI duration in under-fives.

Vitamin A and acute respiratory infections.

By questionnaire we studied the occurrence of acute respiratory infections (ARI) in 1961 children between 0 and 5 years old from a total of 3225 families in Cikutra, Bandung. In 38.7% of them 200.000 IU vitamin A supplement had been given at least once during the preceding year. Mild or moderate ARI occurred in 54.7% of the children during the previous month and in 87.9% during the previous year; severe ARI occurred in 5.5% during the previous month and in 16.8% during the previous year. Surprisingly slightly more ARI occurred in children with vitamin A supplementation. However, vitamin A had been distributed more to low income than high income families, and in the latter group significantly less children suffered from ARI (p less than 0.05; 44% versus 54 a 56%).

Risk factors in smoking habits of high school students.

Although the hazards of smoking is well known, the number of smokers among high school students is still high. There are many factors influencing these students to start smoking. This study was conducted to discover the size of the population of smokers among high school students is still high. There are many factors influencing these students to start smoking. This study was conducted to discover the size of the population of smokers among high school students, their smoking behaviour, and what factors might be associated as risk factors. Questionnaires were filled by 1627 respondents between 12 and 22 years of age of which 955 (58.7%) are boys and 672 (41.3%) are girls. Among all male respondents there were found 622 (86.2%) experimental smokers; among all the girls there were only 99 (13.7%) experimental smokers. From the total number of experimental smokers, 377 (95.2%) boys and 19 (4.8%) girls eventually became smokers. One hundred and seventeen (16.2%) students tried smoking before 13 years old, 65 of these students became smokers. This study found that socio-economic status, parents, friends, and siblings who smoked, and social environment, have significant influence on high school students' smoking habits. To prevent and lower the number of smokers among students in high schools, health and smoking education must be started in the schools as early as possible.