PMID- 31679865
OWN - NLM
STAT- MEDLINE
DCOM- 20210212
LR  - 20210212
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 38
IP  - 3
DP  - 2020 Jan 16
TI  - A phase 1, randomized, observer blind, antigen and adjuvant dosage finding 
      clinical trial to evaluate the safety and immunogenicity of an adjuvanted, 
      trivalent subunit influenza vaccine in adults >/= 65 years of age.
PG  - 578-587
LID - S0264-410X(19)31438-0 [pii]
LID - 10.1016/j.vaccine.2019.10.058 [doi]
AB  - OBJECTIVE: To assess the safety and immunogenicity of the MF59(R)-adjuvanted 
      trivalent influenza vaccine (aTIV; Fluad(R)) compared with modified aTIV 
      formulations. METHODS: A total of 196 subjects >/= 65 years were randomized to 
      receive7different formulations of vaccine containing a range of adjuvant and 
      antigen dosesby single injection, or divided into two injections at a single time 
      point. The primary study objective was to compare the serologic response of 
      different formulations of aTIV containing increased amounts of adjuvant and 
      antigen21 days after vaccination. Subjects were followed for immunogenicity and 
      safety for one year. RESULTS: The highest immune response, as measured by 
      hemagglutination inhibition (HI) assay, 3 weeks after vaccination was observed in 
      subjects in Group 6 with GMT 382.2 (95% confidence interval [CI] 237.5 to 615.0), 
      552.3 (364.8 to 836.1), and 54.1 (36.9 to 79.4) against A/H1N1, A/H3N2, and B 
      respectively. Rates of seroconversion were also generally highest in this 
      treatment group: 75% (95% CI 55.1 to 89.3), 75% (55.1 to 89.3), and 42.9% (24.5 
      to 62.8), respectively, against A/H1N1, A/H3N2, and B strains. The highest 
      incidence of solicited adverse events (AEs) was reported by subjects who received 
      both the highest dosage of antigen in combination with the highest dosage of 
      adjuvant at the same site: 67.9% and 57.1% in Groups 4 and 6, respectively. The 
      majority of solicited AEs were mild to moderate in severity. The number of 
      unsolicited AEs was similar across the different dosages. CONCLUSION: In this 
      phase I trial of adults >/= 65 years of age who received increased adjuvant and 
      antigen dosages relative to the licensed aTIV, increased dosage of MF59 resulted 
      in increased immunogenicity against all 3 components of seasonal influenza 
      vaccine. The increase in immunogenicity was accompanied by an increase in the 
      incidence of local reactogenicity.
CI  - Copyright (c) 2019. Published by Elsevier Ltd.
FAU - Otten, Gillis
AU  - Otten G
AD  - Seqirus Inc., 50 Hampshire Street, Cambridge, MA 02139, United States. Electronic 
      address: Gillis.Otten@Seqirus.com.
FAU - Matassa, Vincent
AU  - Matassa V
AD  - Seqirus Australia, 63 Poplar Road, Parkville, Victoria 3052, Australia. 
      Electronic address: Vince.Matassa@Seqirus.com.
FAU - Ciarlet, Max
AU  - Ciarlet M
AD  - Novartis Vaccines and Diagnostics, 45 Sidney Street, Cambridge, MA 02139, United 
      States.
FAU - Leav, Brett
AU  - Leav B
AD  - Seqirus Inc., 50 Hampshire Street, Cambridge, MA 02139, United States. Electronic 
      address: Brett.Leav@Seqirus.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20191101
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antigens, Viral)
RN  - 0 (Dosage Forms)
RN  - 0 (Influenza Vaccines)
RN  - 0 (MF59 oil emulsion)
RN  - 0 (Polysorbates)
RN  - 7QWM220FJH (Squalene)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage/adverse effects
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, Viral/*administration & dosage/adverse effects/immunology
MH  - Dosage Forms
MH  - Dose-Response Relationship, Immunologic
MH  - Female
MH  - Germany/epidemiology
MH  - Humans
MH  - *Immunogenicity, Vaccine/immunology
MH  - Influenza Vaccines/*administration & dosage/adverse effects/immunology
MH  - Influenza, Human/*epidemiology/immunology/prevention & control
MH  - Male
MH  - Polysorbates/*administration & dosage/adverse effects
MH  - Single-Blind Method
MH  - Squalene/*administration & dosage/adverse effects/immunology
OTO - NOTNLM
OT  - Elderly
OT  - Immunogenicity
OT  - Influenza vaccine
OT  - MF59
OT  - Safety
EDAT- 2019/11/05 06:00
MHDA- 2021/02/13 06:00
CRDT- 2019/11/05 06:00
PHST- 2019/03/28 00:00 [received]
PHST- 2019/10/18 00:00 [revised]
PHST- 2019/10/21 00:00 [accepted]
PHST- 2019/11/05 06:00 [pubmed]
PHST- 2021/02/13 06:00 [medline]
PHST- 2019/11/05 06:00 [entrez]
AID - S0264-410X(19)31438-0 [pii]
AID - 10.1016/j.vaccine.2019.10.058 [doi]
PST - ppublish
SO  - Vaccine. 2020 Jan 16;38(3):578-587. doi: 10.1016/j.vaccine.2019.10.058. Epub 2019 
      Nov 1.