Rotavirus vaccines and the importance of asking tough scientific questions
To the parents of a child who just received a potentially lifesaving vaccination against rotavirus, the molecular biology behind that vaccine may not get much consideration.
Even the medical teams administering vaccinations might not be tuned in to these kinds of minute details. After all, if the vaccine works, isn't that what matters?
Similarly, very few drivers know or care what kind of metal is used on a particular part deep inside their car's engine, as long as the engine functions. But just like a critical automotive component, the molecular biology behind our vaccines determines whether they are successful or not. As new tools are brought to bear on the devastating problem of diarrheal disease, a focus on the molecular biology of rotavirus offers us insight into the complex processes at work inside our bodies and lets us see some of the challenges that lay ahead.
A Question of Diversity
For diseases like measles, there is only one discrete “type” of virus that is recognized by our immune system. While the measles virus is complex, this single, worldwide serotype makes the design, testing and implementation of vaccination strategies more straightforward. Likewise, this uniformity often translates into a high degree of vaccine efficacy: the first dose of measles vaccine produces immunity to the virus in more than 95% of children receiving the vaccine. After two doses, 99% of people are immune to the disease.
Rotavirus, by comparison, is much more diverse in its composition, with many different serotypes circulating worldwide. Two protein components of the rotavirus are combined to define its classification: P types and G types, each of which have 15 different versions. While that makes for a dizzying array of potential virus P-G combinations, five combined P-G types account for more than 95% of rotavirus strains isolated from children.
Many Strains, Many Challenges
This variability makes for more complicated vaccine development, made even more difficult by emergence of different combinations. Recent research shows substantial differences in the circulating serotypes within a population over the span of one year (Payne et al., 2009). If an emerging strain of virus is not represented in a vaccine formulation, a population may not be afforded the same immunological protection from disease. But how do these varying virus compositions occur, and what does it mean for vaccine development?
Like mixing two decks of playing cards, when an animal or human is infected with two or more strains of rotavirus, genome reassortment can result in the exchange of viral components. Some of these new types may not be important to vaccine efficacy -- they may be distinctions without a difference in outcome -- while other types may present novel challenges to the ability of a vaccine to have primed the immune system to mount an effective response. Knowledge of the prevalent rotavirus types is essential for protection.
Measures of Success
Dramatic reductions in hospitalization due to rotavirus have been observed in populations worldwide. Currently available rotavirus vaccines could prevent 74% of rotavirus deaths and 47%-57% of hospitalizations (Munos et al., 2010). Vaccine effectiveness may depend on geographic differences in rotavirus strains, in conjunction with malnutrition and inflammation, common to lower income countries, that ultimately serve to lower vaccine efficacy.
Defeating one of the world's most deadly diseases requires an integrated approach combining vaccine development against enteric pathogens, sanitation strategies, oral rehydration and nutrition. Currently available vaccines promise to make a major contribution to global burden today, if partners work together to bring them to all children. And by continuing to explore the molecular biology of rotavirus, we can ask better scientific questions, deliver better, faster answers and save more lives. Isn't that what matters?
-- Matt Feldman is a PhD Candidate in Human Genetics at The Johns Hopkins University School of Medicine.