A highly attenuated recombinant human respiratory syncytial virus lacking the G protein induces long-lasting protection in cotton rats.
BACKGROUND
Respiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (r)RSV and an rRSV lacking the G gene (DeltaG) were constructed based on a clinical RSV isolate (strain 98-25147-X).


RESULTS
Growth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for DeltaG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days.


CONCLUSIONS
Collectively, the data indicate that a single dose immunization with the highly attenuated DeltaG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since DeltaG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.
Laboratory of Vaccine Research, Netherlands Vaccine Institute, Bilthoven, The Netherlands. Myra.Widjojoatmodjo@nvi-vaccin.nl
Myra N
MN
Widjojoatmodjo
Jolande
J
Boes
Marleen
M
van Bers
Yvonne
Y
van Remmerden
Paul J M
PJ
Roholl
Willem
W
Luytjes
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D008168:Lung / Q000276:immunology / Q000821:virology; D051381:Rats; D011995:Recombination, Genetic; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D016205:Sigmodontinae; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins