PMID- 38091981 OWN - NLM STAT- MEDLINE DCOM- 20240305 LR - 20240313 IS - 1708-8305 (Electronic) IS - 1195-1982 (Print) IS - 1195-1982 (Linking) VI - 31 IP - 2 DP - 2024 Mar 1 TI - A randomized, double-blinded Phase 3 study to demonstrate lot-to-lot consistency and to confirm immunogenicity and safety of the live-attenuated chikungunya virus vaccine candidate VLA1553 in healthy adultsdagger. LID - 10.1093/jtm/taad156 [doi] LID - taad156 AB - BACKGROUND: The global spread of the chikungunya virus (CHIKV) increases the exposure risk for individuals travelling to or living in endemic areas. This Phase 3 study was designed to demonstrate manufacturing consistency between three lots of the single shot live-attenuated CHIKV vaccine VLA1553, and to confirm the promising immunogenicity and safety data obtained in previous trials. METHODS: This randomized, double-blinded, lot-to-lot consistency, Phase 3 study, assessed immunogenicity and safety of VLA1553 in 408 healthy adults (18-45 years) in 12 sites across the USA. The primary endpoint was a comparison of the geometric mean titre (GMT) ratios of CHIKV-specific neutralizing antibodies between three VLA1553 lots at 28 days post-vaccination. Secondary endpoints included immunogenicity and safety over 6 months post-vaccination. RESULTS: GMTs were comparable between the lots meeting the acceptance criteria for equivalence. The average GMT (measured by 50% CHIKV micro plaque neutralization test; muPRNT50) peaked with 2643 at 28 days post-vaccination and decreased to 709 at 6 months post-vaccination. An excellent seroresponse rate (defined as muPRNT50 titre >/= 150 considered protective) was achieved in 97.8% of participants at 28 days post-vaccination and still persisted in 96% at 6 months after vaccination. Upon VLA1553 immunization, 72.5% of participants experienced adverse events (AEs), without significant differences between lots (related solicited systemic AE: 53.9% of participants; related solicited local AE: 19.4%). Overall, AEs were mostly mild or moderate and resolved without sequela, usually within 3 days. With 3.9% of participants experiencing severe AEs, 2.7% were classified as related, whereas none of the six reported serious adverse events was related to the administration of VLA1553. CONCLUSIONS: All three lots of VLA1553 recapitulated the safety and immunogenicity profiles of a preceding Phase 3 study, fulfilling pre-defined consistency requirements. These results highlight the manufacturability of VLA1553, a promising vaccine for the prevention of CHIKV disease for those living in or travelling to endemic areas. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of International Society of Travel Medicine. FAU - McMahon, Robert AU - McMahon R AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Fuchs, Ulrike AU - Fuchs U AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Schneider, Martina AU - Schneider M AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Hadl, Sandra AU - Hadl S AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Hochreiter, Romana AU - Hochreiter R AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Bitzer, Annegret AU - Bitzer A AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Kosulin, Karin AU - Kosulin K AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Koren, Michael AU - Koren M AD - Walter Reed Army Institute of Research, Bethesda, MD, USA. FAU - Mader, Robert AU - Mader R AD - CRETA GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria. FAU - Zoihsl, Oliver AU - Zoihsl O AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Wressnigg, Nina AU - Wressnigg N AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Dubischar, Katrin AU - Dubischar K AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Buerger, Vera AU - Buerger V AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Eder-Lingelbach, Susanne AU - Eder-Lingelbach S AD - Valneva Austria GmbH, 1030 Vienna, Austria. FAU - Jaramillo, Juan Carlos AU - Jaramillo JC AD - Valneva Austria GmbH, 1030 Vienna, Austria. LA - eng GR - 32 European Congress of Clinical Microbiology & Infectious Diseases/ GR - 33 European Congress of Clinical Microbiology and Infectious Diseases/ GR - VLA1553/Coalition for Epidemic Preparedness Innovation/ PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PL - England TA - J Travel Med JT - Journal of travel medicine JID - 9434456 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Vaccines, Attenuated) SB - IM MH - Adult MH - Humans MH - Antibodies, Neutralizing MH - Antibodies, Viral MH - *Chikungunya Fever/prevention & control MH - *Chikungunya virus MH - Double-Blind Method MH - Neutralization Tests MH - Vaccines, Attenuated MH - Adolescent MH - Young Adult MH - Middle Aged PMC - PMC10911060 OTO - NOTNLM OT - Chikungunya virus OT - Phase 3 OT - immunogenicity OT - safety OT - vaccine COIS- R.Mc.M., M.S., U.F., S.H., R.H., A.B., K.K., O.Z., N.W., V.B., K.D., S.E. and J.J. are Valneva employees and own stock and share options in Valneva. M.K. is director, clinical trials centre at Walter Reed Army Institute of Research, Bethesda, MD, USA. R.M. is a scientific consultant for Valneva and has received payments. EDAT- 2023/12/14 00:42 MHDA- 2024/03/05 06:46 PMCR- 2023/12/13 CRDT- 2023/12/13 18:36 PHST- 2023/10/12 00:00 [received] PHST- 2023/12/04 00:00 [revised] PHST- 2023/12/05 00:00 [accepted] PHST- 2024/03/05 06:46 [medline] PHST- 2023/12/14 00:42 [pubmed] PHST- 2023/12/13 18:36 [entrez] PHST- 2023/12/13 00:00 [pmc-release] AID - 7471841 [pii] AID - taad156 [pii] AID - 10.1093/jtm/taad156 [doi] PST - ppublish SO - J Travel Med. 2024 Mar 1;31(2):taad156. doi: 10.1093/jtm/taad156.