Although many high-income countries have regular COVID-19 vaccine booster schedules, there are limited data on the protective effects of some heterologous booster combinations. This observational follow-up study of a double blind randomised controlled parallel group trial evaluates long-term immunogenicity, safety and breakthrough infections to 24 months after booster doses (fractional or standard Pfizer BNT162b2, fractional or standard AstraZeneca ChAdOx1, and standard dose CoronaVac) following CoronaVac and AstraZeneca primary series in healthy adults in Indonesia. Of 1,289 trial participants, 962 (75%) complete follow-up to 24 months. Among CoronaVac-primed participants, responses are lower for fractional than standard dose Pfizer at 28 days (binding IgG geometric mean ratio: 0.75, 95% CI: 0.63-0.90), but differences diminish by 12 and 24 months. AstraZeneca-primed participants have lower initial responses than CoronaVac-primed participants following Pfizer and AstraZeneca boosters. Breakthrough infections occurred in >40% of participants between six and 12 months, and in >35% between 12 and 24 months. Fractional and standard doses of AstraZeneca and Pfizer among CoronaVac-primed or AstraZeneca-primed participants, boost immune responses to 24 months. However, fractional doses elicit lower initial responses than standard doses. These findings provide important information for booster strategies, especially in populations primed with inactivated vaccines. Funding: Coalition for Epidemic Preparedness Innovations (CEPI). Trial registration: ina-registry.org, INA-GO0HLGB.

Introduction: Hepatitis B virus (HBV) infection is a global health problem. Anti-hepatitis B surface antigen (HBsAg) levels increase along with vitamin D levels in adults. However, few studies have examined this relationship in adolescents. Few studies have examined the relationship between vitamin D and HBsAg antibody levels, especially in Indonesia. Methods: This cross-sectional study examined vitamin D and anti-HBsAg levels before and after hepatitis B immunisation. All subjects blood was taken to check for vitamin D level. This study was part of the Safety and Preliminary of Immunogenicity Following Recombinant Hepatitis B (Bio Farma) Vaccine in Adults and Children Phase I trial. Results: This study found that 25-hydroxyvitamin D [25(OH)D] status was primarily deficient based on endocrine criteria. The children’s hepatitis B antibody response was mostly < 10 mIU/mL before and ≥ 10 mIU/mL after vaccination. There was a relationship between sex and 25(OH)D status, with median 25(OH)D levels higher in females (18.2 ng/mL) than in males (9.8 ng/mL). However, the relationship between vitamin 25(OH)D status and anti-HBsAg levels pre- and post-vaccination was not significant. Discussion: However, some research found that vitamin D supplementation after immunisation did not impact vaccine response, several studies have reported that vitamin D can decrease HBV replication through various mechanisms, including reducing viral transcription and interfering with viral protein synthesis. Conclusion: There was no relationship between 25(OH)D status and anti-HBsAg levels. Further research is needed to elucidate the underlying mechanisms and establish optimal treatment strategies.

According to the WHO target product profile for COVID-19 vaccines, the vaccine in development should be indicated for active immunisation in all populations. Therefore, PT Bio Farma developed a candidate vaccine in a subunit protein recombinant platform to help overcome the issue. This trial was an observer-blind, randomised, prospective intervention study. This study targeted individuals who had received complete primary doses of the authorised/approved COVID-19 vaccine. The groups were divided into the primary inactivated vaccine (CoronaVac^®) group, the primary viral vector vaccine (ChAdOx1) group, and the primary mRNA vaccine (BNT162b2) group that received the recombinant protein (IndoVac^®). The groups were compared with the control and primary mRNA vaccine (BNT162b2). The participants enrolled in the study were from two primary care centres in Bandung City and three primary care centres in Denpasar City. A total of 696 participants were enrolled from 1 September to 31 October 2022. The demographic characteristics of the all-vaccine group showed a uniform distribution. The results showed that, compared with the control, the investigational product had inferior effectiveness 14 days after the booster dose was administered. However, 28 days after the booster dose, the investigational product exhibited non-inferior effectiveness compared with the primary groups that received CoronaVac^® (GMR 0.76 (0.57–0.99)) and ChAdOx1 (GMR 0.72 (0.56–59.93)), but the BNT162b2 group (GMR 0.61 (0.39–0.94)) was inferior to the control. At 12 months follow-up after the booster dose, three serious adverse events (SAEs) were reported in three participants, with causality not correlated with the investigated products. Neither AEs of special interest nor severe COVID-19 cases were reported throughout the follow-up period; thus, the IndoVac^® vaccine as a booster was immunogenic and safe. Until the 6-month follow-up after the booster dose, the IndoVac^® vaccine was well tolerated and all reported AEs resolved. This vaccine is registered and can be included in the immunisation programme.

Nearly 3 years after the emergence of COVID-19, it remains one of the world’s problems. COVID-19 vaccination is a priority programme for reducing death and severe symptoms. The primary recombinant novel coronavirus ZF2001 vaccine has gone through Phase III clinical trials and demonstrates efficacy against the highly critical COVID-19 globally and in Indonesia (87.6% and 76.0%, respectively). This study aimed to assess immune persistence after three doses of ZF2001. The study monitored and followed up 400 participants 14 days and 6 months after the third dose and investigated immune persistence 6 months after the phase III vaccination (ZF2001). This study was conducted at recruitment locations in Bandung. Participants were divided into the vaccine and placebo groups and entered into the immunogenicity group. The immune persistence of the vaccine was assessed by measuring geometric mean titres (GMT), neutralising antibodies and seropositivity of IgG anti-S-receptor-binding domain (RBD) after 14 days and 6 months. The seropositive antibody rates were nearly the same between 14 days and 6 months. After 6 months, the GMT, seropositivity of IgG anti-S-RBD and neutralising antibodies in the vaccine group decreased significantly, from 6447.63 to 1514.61 with a P-value of 0.001. A booster was considered important after 6 months.

Brain metastases from cervical cancer are exceedingly rare, with an incidence of 0.4% to 2.3%. Poorly differentiated histologic subtypes, particularly those with lymphovascular space invasion (LVSI) and parametrial involvement, may have a higher propensity for hematogenous spread. Current surveillance protocols do not routinely include brain imaging, potentially leading to delayed diagnosis in patients with early metastases. This case highlights an aggressive presentation of poorly differentiated squamous cell carcinoma (SCC) of the cervix with rapid brain metastases post-treatment, emphasizing the need for revised follow-up and therapeutic strategies. A 46-year-old woman presented with postcoital bleeding and was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIA1 poorly differentiated non-keratinizing SCC of the cervix. She underwent radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy, followed by adjuvant chemoradiotherapy. Despite initial disease control, she developed progressive neurological symptoms five months post-treatment. Brain imaging revealed multiple intracranial metastases, confirmed histologically as metastatic SCC. She un-derwent craniotomy and tumor resection, followed by palliative care due to extensive systemic involvement, including lung metastases. This case highlights the limitations of current surveillance and treatment paradigms in high-risk cervical cancer patients. Earlier imaging and innovative systemic therapies with improved blood-brain barrier penetration may enhance patient outcomes. Future research should focus on refining post-treatment follow-up protocols and integrating novel therapeutic ap-proaches for metastatic cervical cancer.

Adolescents are vulnerable to Coronavirus disease 2019 (COVID-19) infections; thus, their antibodies should be maintained above the protective value. This study aimed to evaluate the immune response and safety to the SARS-CoV-2 protein subunit recombinant vaccine (IndoVac^®) as a heterologous booster dose against COVID-19 in Indonesian adolescents. This open-label prospective intervention study enrolled 150 clinically healthy adolescents aged 12–17 years who had received complete primary doses of the CoronaVac^® vaccine from Garuda Primary Care Centres in Bandung City. The result of immunogenicity was presented with a 95% confidence interval (CI) and analyzed with t-tests from 14 days and 3, 6, and 12 months. The neutralizing antibody geometric mean titers (GMTs) (IU/mL) at baseline and 14 days after booster dose were 303.26 and 2661.2, respectively. The geometric mean fold rises (GMFR) at 3, 6, and 12 months after booster dose were 6.67 (5.217–8.536), 3.87 (3.068–4.886), and 2.87 (2.232–3.685), respectively. Both the neutralizing antibody and IgG antibody were markedly higher in the adolescents than in the adults at every timepoint. The incidence rate of adverse effects (AEs) until 28 days after booster dose was 82.7%, with a higher number of local events reported. Most reported solicited AEs were local pain followed by myalgia with mild intensity. Unsolicited AEs varied with each of the incidence rates < 10%, mostly with mild intensity. Adverse events of special interest (AESI) were not observed. At the 12-month follow-up after the booster dose, four serious adverse events (SAEs) not related to investigational products and research procedures were noted. This study showed that IndoVac^® has a favorable immunogenicity and safety profile as a booster in adolescents and that the antibody titer decreases over time.