METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1.
CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.
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: A sandwich ELISA using B. malayi soluble antigen was employed to detect antifilarial IgG4 antibodies in serum samples of 330 individuals who comprised 88 healthy individuals from nonendemic areas, 15 B. malayi microfilaraemic cases, 22 individuals with soil-transmitted helminthiases, 9 elephantiasis cases and 196 residents from a B. malayi-endemic area. An O.D. value of > 0.420 at serum dilution of 1:400 was used as the cut-off point. This cut-off point was obtained by taking the mean optical density (0.252 + 4 S.E.) of 36 negative sera which had O.D. values greater than 0.1 at serum dilution of 1:400.
RESULTS: All 15 microfilaraemic persons were positive for antifilarial IgG4 antibody. Non-endemic normals, soil-transmitted helminth infected persons and chronic elephantiasis cases were negative for antifilarial IgG4 antibody. Of the 196 individuals from the filaria endemic area, 37 (18.8%) demonstrated presence of antifilarial IgG4 antibodies; and only eight individuals (4.1%) were positive for microfilariae. All eight microfilaraemic individuals were also positive for antifilarial IgG4 antibodies.
CONCLUSION: Antifilarial IgG4-ELISA could detect 4.6 times more positive cases than the microfilaria detection method. With appropriate cut-off values that eliminate cross-reactivities, this serological tool is very useful for Brugia malayi prevalence surveys and diagnosis.