Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.

BACKGROUND: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-µg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose. RESULTS: Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. CONCLUSIONS: In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).

Cost-Effectiveness and Budget Impact Analyses of Pneumococcal Vaccination in Indonesia.

As a country with the high number of deaths due to pneumococcal disease, Indonesia has not yet included pneumococcal vaccination into the routine program. This study aimed to analyse the cost-effectiveness and the budget impact of pneumococcal vaccination in Indonesia by developing an age-structured cohort model. In a comparison with no vaccination, the use of two vaccines (PCV10 and PCV13) within two pricing scenarios (UNICEF and government contract price) was taken into account. To estimate the cost-effectiveness value, a 5-year time horizon was applied by extrapolating the outcome of the individual in the modelled cohort until 5 years of age with a 1-month analytical cycle. To estimate the affordability value, a 6-year period (2019-2024) was applied by considering the government's strategic plan on pneumococcal vaccination. In a comparison with no vaccination, the results showed that vaccination would reduce pneumococcal disease by 1,702,548 and 2,268,411 cases when using PCV10 and PCV13, respectively. Vaccination could potentially reduce the highest treatment cost from the payer perspective at $53.6 million and $71.4 million for PCV10 and PCV13, respectively. Applying the UNICEF price, the incremental cost-effectiveness ratio (ICER) from the healthcare perspective would be $218 and $162 per QALY-gained for PCV10 and PCV13, respectively. Applying the government contract price, the ICER would be $987 and $747 per QALY-gained for PCV10 and PCV13, respectively. The result confirmed that PCV13 was more cost-effective than PCV10 with both prices. In particular, introduction cost per child was estimated to be $0.91 and vaccination cost of PCV13 per child (3 doses) was estimated to be $16.61 and $59.54 with UNICEF and government contract prices, respectively. Implementation of nationwide vaccination would require approximately $73.3-$75.0 million (13-14% of routine immunization budget) and $257.4-$263.5 million (45-50% of routine immunization budget) with UNICEF and government contract prices, respectively. Sensitivity analysis showed that vaccine efficacy, mortality rate, and vaccine price were the most influential parameters affecting the ICER. In conclusion, pneumococcal vaccination would be a highly cost-effective intervention to be implemented in Indonesia. Yet, applying PCV13 with UNICEF price would give the best cost-effectiveness and affordability values on the routine immunization budget.

Immune response of thalassemia major patients in Indonesia with and without splenectomy.

AIM: to describe non-spesific and specific immune response profile in Indonesian thalassemia major with and without splenectomy. METHODS: this study was held at Thalassaemia Centre, Cipto Mangunkusumo Hospital Jakarta on September 2013-February 2014. A comparative cross sectional study was conducted in healthy, thalassemia major aged more than 12 year and seronegative HIV. They were matched in age and sex for splenectomised and non-splenectomised groups, analysing the non-spesific immune response (neutrophil count and phagocytosis) and specific immune response (count and function of cellular immunity). Infection episodes were also analized as immune response in vivo parameter. RESULTS: splenectomised thalassemia major showed increased neutrophil count but significantly decreased non-spesific immune response (neutrophil phagocytosis). Spesific immune response of splenectomised group presented significantly higher absolute lymphocyte, lymphocyte T, CD4+ and CD8+ counts compared to non-splenectomised thalassemia major (p<0.05). Ratio CD4+/CD8+ were similar in these groups. Serum marker of activated cellular imunity function (IL-2 and TNF-) were similar among two groups. Mild infection episodes on splenectomised and non-splenectomised group were 2.02 (ranged 0 to 12) times and 0.81 (ranged 0 to 8) times (p=0.004), respectively. Severe infection on splenectomised group were sepsis for 2 weeks and diarrhea for 1 week, whereas on non-splenectomised group was typhoid fever for 4 days. CONCLUSION: there were significant differences on immune response among thalassemia major patients. Splenectomised thalassemia major showed a greater degree of susceptibility to infections than non-splenectomised thalassemia major.