PMID- 36460535
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20231213
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 41
IP  - 2
DP  - 2023 Jan 9
TI  - A randomized phase 3 trial to assess the immunogenicity and safety of 3 
      consecutively produced lots of freeze-dried MVA-BN(R) vaccine in healthy adults.
PG  - 397-406
LID - S0264-410X(22)01333-0 [pii]
LID - 10.1016/j.vaccine.2022.10.056 [doi]
AB  - Since vaccination remains the only effective protection against orthopox 
      virus-induced diseases such as smallpox or monkeypox, the strategic use and 
      stockpiling of these vaccines remains of significant public health importance. 
      The approved liquid-frozen formulation of Bavarian Nordic's Modified Vaccinia 
      Ankara (MVA-BN) smallpox vaccine has specific cold-chain requirements, while the 
      freeze-dried (FD) formulation of this vaccine provides more flexibility in terms 
      of storage conditions and shelf life. In this randomized phase 3 trial, the 
      immunogenicity and safety of 3 consecutively manufactured lots of the FD MVA-BN 
      vaccine was evaluated. A total of 1129 healthy adults were randomized to 3 
      treatment groups (lots 1 to 3) and received 2 vaccinations 4 weeks apart. For 
      both neutralizing and total antibodies, a robust increase of geometric mean titer 
      (GMT) was observed across all lot groups 2 weeks following the second 
      vaccination, comparable to published data. For the primary results, the ratios of 
      the neutralizing antibody GMTs between the lot group pairs ranged from 0.936 to 
      1.115, with confidence ratios well within the pre-specified margin of 
      equivalence. Results for total antibodies were similar. In addition, 
      seroconversion rates were high across the 3 lots, ranging between 99.1 % and 
      99.7 %. No safety concerns were identified; particularly, no inflammatory cardiac 
      disorders were detected. The most common local solicited adverse events (AEs) 
      reported across lot groups were injection site pain (87.2%) and erythema (73.2%), 
      while the most common general solicited adverse events were myalgia, fatigue, and 
      headache in 40.6% to 45.5% of all participants, with no meaningful differences 
      among the lot groups. No related serious AEs were reported. In conclusion, the 
      data demonstrate consistent and robust immunogenicity and safety results with a 
      freeze-dried formulation of MVA-BN. Clinical Trial Registry Number: NCT03699124.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Turner Overton, Edgar
AU  - Turner Overton E
AD  - Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, 
      AL, United States.
FAU - Schmidt, Darja
AU  - Schmidt D
AD  - Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany.
FAU - Vidojkovic, Sanja
AU  - Vidojkovic S
AD  - Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany.
FAU - Menius, Erika
AU  - Menius E
AD  - Bavarian Nordic Inc., 1005 Slater Road, Suite 101, Durham, NC 27703, United 
      States.
FAU - Nopora, Katrin
AU  - Nopora K
AD  - Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany.
FAU - Maclennan, Jane
AU  - Maclennan J
AD  - Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany.
FAU - Weidenthaler, Heinz
AU  - Weidenthaler H
AD  - Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany. 
      Electronic address: Heinz.Weidenthaler@bavarian-nordic.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT03699124
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20221129
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - TU8J357395 (smallpox and monkeypox vaccine modified vaccinia ankara-bavarian 
      nordic)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Smallpox Vaccine)
RN  - 0 (Vaccines, Attenuated)
SB  - IM
MH  - Humans
MH  - Adult
MH  - *Antibodies, Viral
MH  - *Smallpox Vaccine/adverse effects
MH  - Vaccinia virus
MH  - Vaccines, Attenuated
MH  - Immunogenicity, Vaccine
PMC - PMC9707699
OTO - NOTNLM
OT  - Freeze-dried
OT  - Lot consistency
OT  - MVA-BN
OT  - Modified vaccinia Ankara
OT  - Monkeypox
OT  - Orthopoxvirus
OT  - Smallpox
OT  - Vaccine
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/12/03 06:00
MHDA- 2023/01/04 06:00
PMCR- 2022/11/29
CRDT- 2022/12/02 22:04
PHST- 2022/04/07 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/12/03 06:00 [pubmed]
PHST- 2023/01/04 06:00 [medline]
PHST- 2022/12/02 22:04 [entrez]
PHST- 2022/11/29 00:00 [pmc-release]
AID - S0264-410X(22)01333-0 [pii]
AID - 10.1016/j.vaccine.2022.10.056 [doi]
PST - ppublish
SO  - Vaccine. 2023 Jan 9;41(2):397-406. doi: 10.1016/j.vaccine.2022.10.056. Epub 2022 
      Nov 29.