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Live Attenuated RSVvaccines Collins
Live Attenuated RSVvaccines Collins
(NIAID program)
Peter L. Collins, PhD
National Institute of Allergy and Infectious Diseases
National Institutes of Health, USA
Immunostained RSV filaments on
the surface of a syncytium
NIAID
Objective
Live RSV vaccines to be given to RSV-nave infants
- Based on RSV strain A2 (subgroup A)
- Intranasal administration
Disadvantage
Infectious agent: must attenuate but retain immunogenicity
NS1 NS2
SH
M2
Deletion of RNA regulatory protein yields increased gene transcription, decreased genome
replication
cps2
NS1 NS2
SH
M2
cp
cp
cp cp
(stabilized version of
SH
248
1030
404
rA2cp248/404/1030SH,
stabilized
of Karron et al, 2005) Attenuation mainly involves temperature sensitivity point mutations
cp
NS21313
NS1 NS2
SH
M2
L
1313
NS2
I1314L
HN
Jason McLellan
Barney Graham
Peter Kwong
S290C
DS
(pre-fusion)
DS-Cav1
(pre-fusion)
RSV F protein
S155C
S190F V270L
S290C
FP
TM, CT
Post-fusion
CT
CT
TM
CT
TM CT
S155C
S290C
CT
DS CT
TM CT
DS TM CT
S155C
DS-Cav1 CT
DS-Cav1 TM CT
S190F V270L
S290C
TM
CT
Rhesus study
S155C
S290C
DS
(pre-fusion)
DS-Cav1
(pre-fusion)
N=5
RSV F protein
S155C
S190F V270L
S290C
FP
TM, CT
Post-fusion
CT
Plus: unmodified
F protein control
CT
TM
CT
N=5
TM CT
S155C
S290C
CT
DS CT
TM CT
DS TM CT
S155C
DS-Cav1 CT
DS-Cav1 TM CT
N=4
S190F V270L
S290C
TM
CT
HPIV3-based
vector
HPIV1-, 2-based
vectors
HPIV1, 2
HPIV3
RSV
0
10 11
12 15
18
21
24
age
(months)
LID alumni
Brian Murphy
Steve Whitehead
VRC/NIAID
Jason McLellan
Barney Graham
Peter Kwong
IMPAACT
(International Maternal,
Pediatric, Adolescent,
AIDS Clinical Trials Group)
Coleen Cunningham
Betsy McFarland
George Siberry
Devasena
Gnanashanmugam
Et al.
MedImmune
NIAID Comparative
Medicine Branch