Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults.

OBJECTIVES: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001. METHODS: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017. RESULTS: Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18-55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively. CONCLUSIONS: VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.

An e-registry for household contacts exposed to multidrug resistant TB in Mongolia.

BACKGROUND: The WHO recommends that individuals exposed to persons with multidrug resistant tuberculosis (MDRTB) should be screened for active TB and followed up for 2 years to detect and treat secondary cases early. Resource prioritisation means this is rarely undertaken and where it is performed it's usually using a paper-based record, without collation of data. Electronic data collection into a web-based registry offers the opportunity for simplified and systematic TB contact surveillance with automatic synthesis of data at local, regional and national level. This pilot study was designed to explore the feasibility of usage of a novel e-registry tool and explore obstacles and facilitating factors to implementation. METHODS: In parallel with their paper records, seven dispensaries in Ulaanbaatar, Mongolia collected standardized data electronically using Open Data Kit (ODK). Patients with MDRTB and their contacts were recruited during a single clinic visit. Staff and patients were interviewed to gain insights into acceptability and to identify areas for improvement. RESULTS: Seventy household contacts of 32 MDR-TB index patients were recruited. 7/70 contacts (10%) traced had active TB at the time they were recruited to the e-registry. Paper registry satisfaction was low; 88% of staff preferred the e-registry as it was perceived as faster and more secure. Patients and their contacts were generally supportive of the e-registry; however, a significant minority 10/42 (24%) of index cases who were invited, declined to participate in the e-registry, with data security cited as their top concern. CONCLUSION: E-registries are a promising tool for MDRTB contact tracing, but their acceptability amongst patients should not be taken for granted.