Vaccine potential of prokaryotically-expressed fragments of the respiratory syncytial virus (RSV) F and G proteins

by Mader, David

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneurnonia in infants, children, the elderly and immunocompromised. To investigate immune responses to various RSV proteins, previously constmcted recombinant proteins consisting of Fragments of the RSV G-protein and a portion of the E. coli thioredoxin protein (Tm-G128-229, Tm-G128- 188, Trx-G189-229) along with a newly cloned fragment of the RSV F-proiein (Ta-F164-357) were evaluated in animal models. Of these four protein fragments, Tm-G128-229was the most effective in eliciting neutralizing antibodies in rabbits. Tm-G128-229 was chosen for extensive studies of vaccine evaluation in BALB/c mice. Intranasal immunization of BALB/c mice with Trx- G128-229 followed by RSV challenge led to a significant reduction in RSV replication, which was fùrther reduced when Tm-G128-229 was encapsulated in liposomes. This reduction in RSV replication coincided with an increase in RSV-specific IgG serum antibodies and RSV-neutralizing antibodies. Immunization with unencapsulated Trx- G128-229 followed by RSV challenge led to a significant increase in the level of both eosinophils and neutrophils in bmnchoalveoIar lavage fluids of mice, while immunization with liposome-encapsulated Tm-(3128-229 significantly reduced this increase. In addition, similar levels of pulmonary cellular infiltration resulted fiom immunization with either unencapsulated or liposome-encapsulated Tm-G128-229. Collectively, these results show the potential of using liposomes combined with certain prokaryoticallyexpressed fragments of the RSV G-protein as a novel immunization strategy against RSV infection.