PMID- 31796225
OWN - NLM
STAT- MEDLINE
DCOM- 20210226
LR  - 20210226
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 38
IP  - 5
DP  - 2020 Jan 29
TI  - A study to evaluate the immunogenicity and shedding of live attenuated influenza 
      vaccine strains in children 24-<48 months of age.
PG  - 1001-1008
LID - S0264-410X(19)31597-X [pii]
LID - 10.1016/j.vaccine.2019.11.055 [doi]
AB  - BACKGROUND: Quadrivalent live attenuated influenza vaccine (LAIV4) showed reduced 
      effectiveness against the A/H1N1 component in the 2013-2014 and 2015-2016 
      influenza seasons. The most likely cause of reduced LAIV effectiveness against 
      A(H1N1)pdm09 strains was poor intranasal replication. OBJECTIVES: To compare the 
      immunogenicity and shedding of a new A/H1N1 strain (A/Slovenia), to a A/H1N1 
      strain known to have reduced effectiveness (A/Bolivia). PATIENTS/METHODS: This 
      was a randomized, double-blind, multicenter study. Children aged 24-<48 months of 
      age were randomized 1:1:1 to receive two doses of LAIV4 2017-2018 
      (LAIV4(A/Slovenia)), or LAIV4 2015-2016 or trivalent LAIV (LAIV3) 2015-2016 
      formulations (LAIV4(A/Bolivia) or LAIV3(A/Bolivia), respectively) on days 1 and 
      28. The primary endpoint was strain-specific hemagglutination inhibition (HAI) 
      antibody seroresponse at 28 days post each dose, and secondary endpoints included 
      immunogenicity, shedding, and safety. Solicited symptoms, adverse events (AEs), 
      and serious AEs (SAEs) were recorded. Pre-specified statistical testing was 
      limited to the primary endpoint of HAI antibody responses. RESULTS: A total of 
      200 children were randomized (median age 35.3 months; 53% male; 57% had 
      previously received influenza vaccine). Significantly higher HAI antibody 
      responses for the A/Slovenia strain were observed after Dose 1 and Dose 2. 
      Neutralizing antibodies and nasal immunoglobulin A antibody responses were higher 
      for A/Slovenia versus A/Bolivia. More children shed the A/Slovenia vaccine strain 
      than the A/Bolivia strain on Days 4-7 after Dose 1. No deaths, SAEs, or 
      discontinuations from vaccine occurred. CONCLUSIONS: The new A(H1N1)pdm09 
      A/Slovenia LAIV strain demonstrated improved immunogenicity compared with a 
      previous strain with reduced effectiveness and induced immune responses 
      comparable to a highly efficacious pre-pandemic H1N1 LAIV strain. These results 
      support the use of LAIV4 containing A/Slovenia as a vaccine option in clinical 
      practice.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Mallory, Raburn M
AU  - Mallory RM
AD  - MedImmune, Gaithersburg, MD, USA. Electronic address: malloryr@MedImmune.com.
FAU - Nyborg, Andrew
AU  - Nyborg A
AD  - MedImmune, Gaithersburg, MD, USA.
FAU - Kalyani, Rubana N
AU  - Kalyani RN
AD  - MedImmune, Gaithersburg, MD, USA.
FAU - Yuan, Yuan
AU  - Yuan Y
AD  - MedImmune, Gaithersburg, MD, USA.
FAU - Block, Stan L
AU  - Block SL
AD  - Kentucky Pediatrics and Adult Research Inc., Bardstown, KY, USA.
FAU - Dubovsky, Filip
AU  - Dubovsky F
AD  - MedImmune, Gaithersburg, MD, USA.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20191130
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Viral)
RN  - 0 (Influenza Vaccines)
RN  - 0 (Vaccines, Attenuated)
SB  - IM
MH  - Antibodies, Viral/blood
MH  - Child, Preschool
MH  - Double-Blind Method
MH  - Female
MH  - Hemagglutination Inhibition Tests
MH  - Humans
MH  - *Immunogenicity, Vaccine
MH  - Influenza A Virus, H1N1 Subtype/immunology
MH  - Influenza Vaccines/*administration & dosage
MH  - *Influenza, Human/prevention & control
MH  - Male
MH  - Vaccines, Attenuated/administration & dosage
MH  - *Virus Shedding
OTO - NOTNLM
OT  - Live attenuated influenza vaccine
OT  - Pediatric
OT  - Seasonal influenza
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Raburn M. Mallory, Rubana N. Kalyani, Yuan Yuan and Filip Dubovsky are 
      employees and shareholders of MedImmune/AstraZeneca. Stan L. Block received 
      research grants from AstraZeneca. Andrew Nyborg is a former employee and 
      shareholder of MedImmune/AstraZeneca.
EDAT- 2019/12/05 06:00
MHDA- 2021/02/27 06:00
CRDT- 2019/12/05 06:00
PHST- 2019/03/01 00:00 [received]
PHST- 2019/10/09 00:00 [revised]
PHST- 2019/11/20 00:00 [accepted]
PHST- 2019/12/05 06:00 [pubmed]
PHST- 2021/02/27 06:00 [medline]
PHST- 2019/12/05 06:00 [entrez]
AID - S0264-410X(19)31597-X [pii]
AID - 10.1016/j.vaccine.2019.11.055 [doi]
PST - ppublish
SO  - Vaccine. 2020 Jan 29;38(5):1001-1008. doi: 10.1016/j.vaccine.2019.11.055. Epub 
      2019 Nov 30.