Novel RSV Vaccines Under Development Barney S. Graham, M.D., Ph.D. Achievements and Future Challenges in the Surveillance of Respiratory Viruses San Jose, Costa Rica January 30, 2013

Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Department of Health and Human Services

For more information: 1-866-833-LIFE vrc.nih.gov [email protected]

RSV Genome Organization and Protein Functions le

P

NS1 NS2 N

F

M SH G

M2-1 M2-2

L

3´

tr 15,222 nt total

0

2

4

8

6

10

plasma membrane

15 kb

envelope spikes G (298) - attachment

nonstructural

NS1 (139) - inhibit Type I IFN induction NS2 (124) - inhibit Type I IFN signaling - activate PI3K and NF-B - inhibit apoptosis

150 nm

nucleocapsid-associated regulatory M2-2 (90) - viral transcription  - RNA replication 

N (391) - RNA-binding P (241) - phosphoprotein L (2165) - polymerase M2-1 (194) - transcription processivity factor

- neutralization and protective antigen - antibody decoy (secreted G) - fractalkine mimic - TLR antagonist F (574) - fusion and entry - neutralization and protective antigen - TLR4 agonist

SH (64) - putative viroporin - inhibits apoptosis

inner envelope face M (256) - assembly 2

Disease Severity is Greatest in Children