Alphavirus replicon particles encoding the fusion or attachment glycoproteins of respiratory syncytial virus elicit protective immune responses in BALB/c mice and functional serum antibodies in rhesus macaques.
Respiratory syncytial virus (RSV) is a major cause of acute respiratory tract disease in humans. Towards development of a prophylactic vaccine, we genetically engineered Venezuelan equine encephalitis virus (VEEV) replicons encoding the fusion (Fa) or attachment (Ga or Gb) proteins of the A or B subgroups of RSV. Intramuscular immunization with a formulation composed of equal amounts of each replicon particle (3vRSV replicon vaccine) generated serum neutralizing antibodies against A and B strains of RSV in BALB/c mice and rhesus macaques. When contrasted with purified natural protein or formalin-inactivated RSV formulated with alum, the 3vRSV replicon vaccine induced balanced Th1/Th2 T cell responses in mice. This was evident in the increased number of RSV-specific IFN-gamma(+) splenocytes following F or G peptide stimulation, diminished quantity of eosinophils and type 2 T cell cytokines in the lungs after challenge, and increased in vivo lysis of RSV peptide-loaded target cells. The immune responses in mice were also protective against intranasal challenge with RSV. Thus, the replicon-based platform represents a promising new strategy for vaccines against RSV.
Elliott
Matthew B
MB
Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. elliotm2@wyeth.com
Chen
Tong
T
Terio
Nicole B
NB
Chong
Siew-Yen
SY
Abdullah
Rashed
R
Luckay
Amara
A
Egan
Michael A
MA
Boutilier
Lee Anne
LA
Melville
Krista
K
Lerch
Robert A
RA
Long
Deborah
D
Eldridge
John H
JH
Parks
Christopher L
CL
Udem
Stephen A
SA
Hancock
Gerald E
GE
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000276:immunology*; D005260:Female; D007273:Injections, Intramuscular; D008168:Lung / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D016207:Cytokines; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D014765:Viral Vaccines