Oligodeoxynucleotides containing certain unmethylated CpG sequences (CpG ODN) are powerful immunostimulants when co-administered with a variety of antigens, making them attractive adjuvants for prophylactic (e g infectious diseases) and therapeutic (e.g. cancer) vaccines. In addition to being useful when administered parenterally, they are also effective when applied topically to mucosal tissues. This makes them potentially useful in development of a respiratory syncytial virus (RSV) vaccine that would be heat-stable and would not require sterile needles and syringes. In addition to use in this country, such a vaccine would have enormous utility in developing countries, where the disease burden of RSV is the highest and where lack of refrigeration and sterile needles and syringes preclude other approaches. In preliminary studies we have shown that purified fusion glycoprotein (F) from RSV is not immunogenic when administered intranasally without an adjuvant; however, co-administration of F and CpG ODN (F/CpG) stimulated a highly effective immune response in the lungs of cotton rats. While this result was highly encouraging, the lungs of protected animals showed atypical histopathology reminiscent of that seen with an earlier, formalin-inactivated (FI-RSV) vaccine. Our published work on FI-RSV demonstrated that the histologic phenotype associated with vaccine-enhanced disease could be eliminated by the addition of monophosphoryl lipid A (MPL), and thus we believe that the atypical histopathology accompanying F/CpG immunization can also be eliminated through use of supplements. The goal of this Phase I application is to characterize the cytokine, chemokine and cellular responses to F/CpG, comparing them to primary RSV infection and to immunization with FI-RSV. Phase II activities would use that information to formulate a vaccine that would be both effective and safe.
Thesaurus Terms: CpG island, Pneumovirus vaccine, active immunization, chimeric protein, glycoprotein, immunity, respiratory syncytial virus, vaccine development chemokine, cytokine, drug screening /evaluation, oligonucleotide histopathology, laboratory rat
