By David N. Leff
Of some 150 respiratory system viruses out there, two are the principal pathogens thatput children under two years of age into the hospital. They are respiratory syncytialvirus (RSV) and parainfluenza virus type 3 (PIV3). Unlike many infectious diseases ofchildhood, there are no vaccinations protecting against this pair of RNA paramixoviruses,which account for one-third of all hospitalization for respiratory diseases in pediatricsubjects.
Virologists at the National Institute of Allergy and Infectious Disease (NIAID) aredeploying the new tools and techniques of molecular biology to develop live attenuatedvirus vaccines to ward off these twin viral causes of infant pneumonia, bronchiolitis andcroup (laryngotracheobronchitis).
Having cloned and sequenced each of the two viral genomic RNA in toto, and donemuch of the work to construct a complete cDNA copy of each, the respiratory virus sectionof NIAID's laboratory of infectious diseases is shopping for an industrial partner toproduce replication-competent RSV and PIV3 from DNAs encoding these complete copies, andgo on to create commercial vaccines.
Huge Market for Pediatric Vaccines
Two weeks ago, the NIH Office of Technology Transfer (OTT) forwarded a notice to the FederalRegister announcing “opportunity for a Cooperative Research and DevelopmentAgreement (CRADA)“ for a commercial company to come forward with scientific staff andfunding to create human-friendly vaccines, and move them into clinical trials and on tomarket.
“The prospective market is huge,“ OTT licensing specialist Harold Saffersteintold BioWorld.
To which virologist Brian Murphy, who heads the respiratory virus lab, added:“Every kid is a candidate for vaccination against RSV and PIV3. These would beincorporated in their routine immunizations.“
He cites an estimated 50,000 hospitalizations a year of very young children, for anaverage stay of one to two weeks. “Mortality is low in normal infants,“ Murphytold BioWorld, “but high (20 to 50 percent) in those with congenital heartdisease or bronchopulmonary dysplasia.“
The reason no vaccine for either RSV or PIV3 exists today, Murphy explained, is that inthe 1960s an inactivated RSV vaccine tried in children backfired, by exacerbating ratherthan alleviating the infective symptoms. Besides a better understanding of the immunologyinvolved, he said, “Two major changes now make it possible.“ One is thesuccessful use of continuous Vero cell lines; the other, the ability to do large-scalescreening and selection of viral strains with desirable characteristics.
“But the subject of this particular CRADA request,“ Murphy added,“involves a brand new technique, namely, clones of cDNA that are complete copies ofthe RSV and PIV3 genomes. These can be used to make RNA transcripts in tissue culture, inthe presence of helper viruses to rescue them.“
Now, he added, “we are looking for an industrial partner who would be able to puta relatively large effort into optimizing these systems, so we can not only rescue thegenome, but also introduce and test the number of mutations that are going to be necessaryto introduce into the wild-type virus, so they can be sufficiently attenuated for use in avaccine.“
Murphy allowed, “I am aware of two nibbles from candidat CRADA companies. Both are small biotechnology firms; we're hoping perhaps for more.“
OTT's Safferstein pointed out that “the project comes with a number of backgroundpatents that we own,“ and added, “if any intellectual property was to come outof a CRADA with industry, then the partner would have an option to get an exclusivelicense for it.“