rotavirus and Jennerian method

In March 2016, I listened to an episode of What’s The Point podcast by FiveThirtyEight featuring Dr. Rebecca Grais from the Doctors Without Borders (Médecins Sans Frontières, MSF). It was specifically on the rotavirus infection that could cause a debilitating episode of diarrhea especially in poor countries like Niger. The thing is we do have vaccines against rotavirus but they are expensive and require cold chain storage.

Poor countries do not have access to a cold chain (no electric, so that’s tough) and engineers are teaming up with biomedical researchers to come up with solutions. Oddly enough, I received an alert from the Vaccine journal featuring current developments in cold chain for vaccine deployment.

Engineers come up with technologies to keep vaccines cold for a long-term storage. But still, biomedical researchers need to figure out how to deploy vaccines if cold chain is still expensive. Also, couple days ago I received a newsletter from NPR Goat and Soda and guess what, Rebecca Grais was mentioned. Researchers found a brilliant way to deliver the live-attenuated rotavirus vaccine without cold chain: freeze-dry it and suck up the liquid (a.k.a lyophilized). To use it, just dissolve the powder and consume it orally.

A phase 3 trial was conducted in Niger to evaluate the safety and efficacy of the vaccine, BRV-PV (bovine rotavirus pentavalent vaccine). It was a success. BRV-PV confers a protection against severe gastroenteritis caused by rotavirus infection. This is the report on the clinical trial published on NEJM. The vaccine was developed at the Serum Institute of India. I followed the paper to learn more about the vaccine design because I had this question: why use the bovine version of the rotavirus? Enter, the Jennerian concept of vaccine design.

The Jennerian concept dictates as follows in this case: immunization with animal rotaviruses considered to be naturally attenuated for humans. What does this mean? Say that if you want to go with the human version of rotaviruses, you need to carefully weaken the viruses so that when you administer it as a vaccine, it wouldn’t cause an outbreak. And sometimes, the process of attenuating viruses could be cumbersome therefore the price could go up. But if you go with the animal version of the virus, our immune system is powerful enough to prevent it from becoming a threat while at the same time conferring protection against any future outbreak.

Here in this case, the researchers came up with a modified Jennerian approach. Instead of going straight with the bovine rotaviruses, they modified the viruses to express a certain glycoprotein that exists on human rotaviruses. In short, the bovine rotaviruses were engineered. Globally, there are five different human rotaviruses circulating that account for 88% of all strain and those are the G1, G2, G3, G4, and G9 strains, with G1 and G2 being the most prevalent. Let’s talk about that special glycoprotein. In rotavirus research, it is a consensus that the presence of VP7 glycoprotein is important for protection. Armed with all these information, the VP7 glycoprotein from G1-G4, G9 strains of human rotaviruses are engineered into the bovine rotavirus, creating the pentavalent vaccine.

How do you know the vaccine is a success? You sample the stool. You gotta deal with some shit, literally. If there is an outbreak, you would expect viral particles in stool. If the vaccine is working in the sense that it mounts immune response thus neutralizing it, you would expect no viral particles in stool.