METHODS: EU-COVAT-1-AGED Part A is a randomised controlled, adaptive, multicentre phase II trial evaluating safety and immunogenicity of a 3rd vaccination (1st booster) in individuals ≥75 years. Fifty-three participants were randomised to full-doses of either mRNA-1273 (Spikevax®, 100 µg) or BNT162b2 (Comirnaty®, 30 µg). The primary endpoint was the rate of 2-fold circulating antibody titre increase 14 days post-vaccination measured by quantitative electrochemiluminescence (ECL) immunoassay, targeting RBD region of Wuhan wild-type SARS-CoV-2. Secondary endpoints included the changes in neutralising capacity against wild-type and 25 variants of concern at 14 days and up to 12 months. Safety was assessed by monitoring of solicited adverse events (AEs) for seven days after on-study vaccination. Unsolicited AEs were collected until the end of follow-up at 12 months, SAEs were pursued for a further 30 days.
RESULTS: Between 08th of November 2021 and 04th of January 2022, 53 participants ≥75 years received a COVID-19 vaccine as 1st booster. Fifty subjects (BNT162b2 n = 25/mRNA-1273 n = 25) were included in the analyses for immunogenicity at day 14. The primary endpoint of a 2-fold anti-RBD IgG titre increase 14 days after vaccination was reached for all subjects. A 3rd vaccination of full-dose mRNA-1273 provided higher anti-RBD IgG titres (Geometric mean titre) D14 mRNA-127310711 IU/mL (95 %-CI: 8003;14336) vs. BNT162b2: 7090 IU/mL (95 %-CI: 5688;8837). We detected a pattern showing higher neutralising capacity of full-dose mRNA-1273 against wild-type as well as for 23 out of 25 tested variants.
INTERPRETATION: Third doses of either BNT162b2 or mRNA-1273 provide substantial circulating antibody increase 14 days after vaccination. Full-dose mRNA-1273 provides higher antibody levels with an overall similar safety profile for people ≥75 years.
FUNDING: This trial was funded by the European Commission (Framework Program HORIZON 2020).
METHODS: In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies.
RESULTS: Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection.
CONCLUSIONS: The rVSV vectors expressing Nipah virus G or F are prime candidates for new 'emergency vaccines' to be utilized for NiV outbreak management.
METHODS: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating.
RESULTS: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017.
CONCLUSION: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.
METHODS: A survey was distributed to national experts in infectious diseases and health-care authorities (March 2015-April 2016), collecting information on local recommendations, costs and perception of barriers for implementation.
RESULTS: Forty-nine of the 79 contacted countries (62% response rate) provided a complete analyzable data. RVI was recommended in 27/49 countries (55%). Although five countries have recommended RVI since 2006, a large number (16, 33%) included RVI in a National Immunization Schedule between 2012 and 2014. The costs of vaccination are covered by the government (39%), by the GAVI Alliance (10%) or public and private insurance (8%) in some countries. However, in most cases, immunization is paid by families (43%). Elevated cost of vaccine (49%) is the main barrier for implementation of RVI. High costs of vaccination (rs=-0.39, p=0.02) and coverage of expenses by families (rs=0.5, p=0.002) significantly correlate with a lower immunization rate. Limited perception of RV illness severity by the families (47%), public-health authorities (37%) or physicians (24%) and the timing of administration (16%) are further major barriers to large- scale RVI programs.
CONCLUSIONS: After 10years since its introduction, the implementation of RVI is still unacceptably low and should remain a major target for global public health. Barriers to implementation vary according to setting. Nevertheless, public health authorities should promote education for caregivers and health-care providers and interact with local health authorities in order to implement RVI.
METHODS: Vaccination impact was investigated with an age-structured, host-vector, serotype-specific compartmental model. Parameters related to vaccine efficacy and levels of dengue transmission were estimated using data collected during the phase III efficacy studies. Several vaccination programs, including routine vaccination at different ages with and without large catch-up campaigns, were investigated.
RESULTS: All vaccination programs explored translated into significant reductions in dengue cases at the population level over the first 10years following vaccine introduction and beyond. The most efficient age for vaccination varied according to transmission intensity and 9years was close to the most efficient age across all settings. The combination of routine vaccination and large catch-up campaigns was found to enable a rapid reduction of dengue burden after vaccine introduction.
CONCLUSION: Our analysis suggests that dengue vaccination can significantly reduce the public health impact of dengue in countries where the disease is endemic.
METHODS: Following ethical approval, we conducted hospital-based dengue surveillance for one year in three referral hospitals. Suspected cases aged 9-25 years underwent dengue virological confirmation by RT-PCR and/or NS1 Ag ELISA at a central laboratory. Two age- and geography-matched hospitalized non-dengue case-controls were recruited for a traditional CC study. Suspected cases testing negative were test-negative controls. Socio-demographic, risk factor and routine laboratory data were collected. Logistic regression models were used to estimate associations between confirmed dengue and risk factors.
RESULTS: We recruited 327 subjects; 155 were suspected of dengue. The planned sample size was not met. 124 (80%) of suspected cases were dengue-confirmed; seven were assessed as severe. Three had missing RT-PCR results; the study recruited 28 test-negative controls. Only 172 matched controls could be recruited; 90 cases were matched with ≥1 controls. Characteristics of cases and controls were mostly similar. By CC design, two variables were significant risk factors for hospitalized dengue: recent household dengue contact (OR: 54, 95% CI: 7.3-397) and recent neighbourhood insecticidal fogging (OR: 2.1; 95% CI: 1.3-3.6). In the TN design, no risk factors were identified. In comparison with gold-standard diagnostics, routine tests performed poorly.
CONCLUSIONS: The CC design may be more appropriate than the TN design for hospitalized dengue vaccine effectiveness studies. Selection bias in case control selection could be minimized by protocol changes more easily than increasing TN design control numbers, because early-stage dengue diagnosis in endemic countries is highly specific. MREC study approval: (39)KKM/NIHSEC/P16-1334.
METHODS: We conducted a health facility-based cross-sectional study in Aceh and West Sumatra province from 1 February to 13 June 2018. Patients who visited outpatient departments, have had children or were expecting their first child, were approached and interviewed to collect information on acceptance, WTP, demographic and socio-economic variables and attitudes towards childhood vaccines. Associations of explanatory variables influencing acceptance and WTP were assessed using logistic regression and linear regression analysis, respectively.
RESULTS: In total, 956 respondents were included in the final analysis of acceptance, of whom 338 (35.3%) expressed their WTP. We found that 757 (79.1%) of the respondents were likely to be vaccinated and to recommend their partner to be vaccinated. Higher educational attainment, having a job, having heard about Zika and a good attitude towards childhood vaccination were associated with ZV acceptance in the univariate analyses. In the multivariate analysis, attitude towards childhood vaccination was the strongest predictor for ZV vaccination. We found the geometric mean and median of WTP was US$ 13.1 (95% CI: 11.37-15.09) and US$ 7.0 (95% CI: 4.47-10.98), respectively. In the final model, having heard about Zika, having a job, and higher income were associated with a higher WTP.
CONCLUSION: Although the acceptance rate of the ZV is relatively high in Indonesia, less than 40% of respondents are willing to pay, underscoring the need for a low-cost, high-quality vaccine and public sector subsidies for Zika vaccinations in the country.