Vaccine Approaches

Despite the fact that the correlates of immunity against rotavirus are still not entirely understood, much progress has been made in vaccine development. Ideally a vaccine would provide sterilizing immunity against its target pathogen, but in the case of rotavirus this has proved difficult to achieve and is not necessary to markedly reduce mortality and morbidity due to infection.

Previous infection with rotavirus does not confer sterilizing immunity on an individual, but the reduced severity of subsequent infections has provided researchers a promising place to begin. The goal of the vaccines that are currently being developed is to mimic the effect of initial infection without actually causing the illness associated with viral replication.

Vaccine Type

Live attenuated vaccines

Most of the work surrounding rotavirus vaccination has centered on live attenuated vaccines, based on either human rotavirus or an animal strain of the virus. Objections to live vaccines center around the possibility of an attenuated strain reverting to a virulent strain of the virus. Because most cases of rotavirus are resolved without treatment, and severe infections can be treated effectively assuming the facilities and resources are available, a live attenuated rotavirus vaccine does not pose as much of a risk as an attenuated vaccine for a more serious, unresolvable pathogen such as HIV.

Live attenuated vaccines are useful because they can induce an immune response most akin to the unaltered virus. Infection with a live vaccine stimulates the same branches of the immune system as a natural infection by replicating in the host's body and leads to a similar level of resistance to severe re-infection.

The initial success of RotaShield^®, a tetravalent human-rhesus reassortant vaccine, before its subsequent withdrawl from the market has led to continued interest in live attenuated vaccines as very promising possibilities. RotaTeq^® and Rotarix^®, the two vaccines that are currently in FDA approved Phase III trials in the United States, are both attenuated live vaccines.

DNA Vaccine

DNA vaccines are another possibility in the effort to develop an effective vaccine against rotavirus.   DNA vaccines are intended to stimulate both branches of the immune system, like the attenuated live vaccines, without the risk of the reactivation of the vaccine strain.   A variety of DNA vaccines have been attempted for rotavirus[1], with some efficacy evident in mice trials.   DNA coding for VP4, VP6 and VP7 has been delivered both orally [2] and by gene gun [3].   However, the success of live attenuated or reassortant vaccines has stifled interest in DNA vaccines which are more likely to be expensive and are harder to manufacture. These characteristics of DNA vaccines make them less useful in developing countries where the vaccine is most needed.  

Subunit Vaccine

Virus-like particles (VLPs) are being developed as another possible vaccine. Trials in murine models using rotavirus-like particles containing G1 VP7 have been promising, inducing both homotypic and heterotypic serum neutralizing immune responses.[6] Further research in this area is necessary.

Delivery

Most vaccines that have been developed or are in the pipeline are orally delivered. This method of delivery parallels the oral-fecal pathway of natural infection. It allows the vaccine to be delivered directly to the gastrointestinal system. In the case of a live attenuated vaccine, the attenuated virus then replicates in the gut and stimulates an immune response similar to that of normal viral infection, inducing both a humoral and a cell-mediated response.

Testing for Efficacy

The efficacy and immunogenicity of various vaccine candidates are tested in a number of ways. Stools are collected from vaccinated individuals and examined for rotavirus antigen by EIA[5]. Blood samples from vaccinated individuals are collected before and after vaccination and assayed for stereotype-specific neutralizing rotavirus antibody. Fecal shedding of the attenuated virus of a live vaccine is also a measure of vaccine take.