A small segment of viral protein 4 (VP4), a key component of the outer coat of the human rhinovirus, is highly conserved among 100 rhinovirus serotypes, and antibodies raised against this component inhibit several different strains of this "common cold" virus, according to Thomas Smith of the Donald Danforth Plant Science Center in St. Louis, Mo., and his collaborators. These findings thus raise the possibility and renew hopes of developing a broad-spectrum vaccine to protect humans against the common cold, says Marianne Manchester of the Scripps Research Institute in La Jolla, Ca., who was not involved in this rhinovirus research. A report detailing the promising findings appears in the July 2009 Journal of Virology (83:7040-7048).  

About a decade ago, Smith learned that part of VP4 is extruded and transiently exposed externally from the viral surface as part of a viral-protein flexing phenomenon that he calls "breathing." Much the same thing occurs with other picornaviruses, including poliovirus and cocksackievirus, he points out. The flexing of VP4 could mark viral readiness to interact with host cell membrane receptors, a crucial early step in the infective process.  

In the case of V4 from rhinovirus, antibodies raised to this extruded protein segment inhibit not only the same but also several different strains of this common cold-causing virus, according to Smith. His collaborator Philip R. Dormitzer of Novartis calls this antibody response the "most intriguing" finding in rhinovirus vaccine research in years.  

In their recent experiments, the investigators were intent on studying fundamental structural changes at the molecular level. With that in mind, they caught "the virus with the VP4 exposed to see if we could obtain some structural information," Smith says. They also used that VP4 peptide segment as an antigen to raise antibodies.  

"We found that these antibodies inhibited infection of several different rhinovirus serotypes," he says. "This region of the virus is nearly identical in all 100 strains of rhinovirus-far, far more conserved than any other part of the virus. So while we were really going after the fundamental science of the virus and how it interacts with the target cell for infection, we came upon a way to possibly make a vaccine for the common cold."  

"We are still a long way from a rhinovirus vaccine," Dormitzer cautions. "The breadth of neutralization is impressive, but the neutralizing titers thus far are low, and neutralization of virus in vitro does not guarantee protection from illness." However, because VP4 is so highly conserved, it is less likely that antibody-resistant viral mutants will arise to a VP4-based vaccine because this segment appears too critical for such viral mutants to be infective. There are good reasons to pursue such a vaccine, even though common colds are mainly an annoyance for the majority of the population, Dormitzer continues. Thus, among some population groups, such infections can prove more serious. For example, rhinovirus infections can trigger asthma attacks and may exacerbate chronic obstructive pulmonary disease, both of which are serious conditions and potentially life threatening, he points out.

David Holzman
David Holzman is the Microbe Journal Highlights Editor.