A new study shows that the effectiveness of current vaccines against porcine reproductive and respiratory syndrome virus (PRRSV) is due to the response of T cells against the disease, rather than the production of antibodies. The work is an important step in identifying specific targets for vaccines on a rapidly mutating virus.
PRRSV is a common and costly disease in pigs that is estimated to cause losses of over $1 billion annually to the pork industry. While current vaccines offer protection, the rapid mutation of PRRSV means that vaccinated pigs cannot produce a consistent or effective broadly neutralizing antibody response.
Antibodies are proteins that "tag" pathogens for destruction by the immune system. T cells are part of the immune system that eliminate infected cells where more viruses are made and help the body remember what those pathogens look like. Vaccines work by stimulating the body to produce antibodies and T cells against the pathogen so that the immune system can identify and destroy it before it gains a foothold and causes clinical disease.
"PRRSV is one of the fastest mutating RNA viruses in the veterinary world," says Michael Rahe, assistant professor of population health and pathobiology at North Carolina State University's College of Veterinary Medicine. "That means that any neutralizing antibodies developed from vaccination typically do not match circulating strains.
"We know that vaccines confer some protection against PRRSV, but because of this mismatch between antibody response and virus, we need to understand exactly what part of the immune system is providing this protection."
Rahe is the corresponding author of the study and began the work while at Iowa State University.
The researchers looked at four groups of pigs: an unvaccinated and unchallenged group (strict negative control); an unvaccinated and PRRSV challenged group; one group that had been vaccinated with the one of the most used PRRSV vaccines and then challenged with PRRSV; and a group that also received the PRRSV vaccine in combination with another vaccine against porcine circovirus 2 and then also challenged with PRRSV.
Using direct detection techniques to characterize both the PRRSV infection as well as the immune response, they found that all vaccinated groups - whether they received an individual or combination vaccine - had an elevated PRRSV-specific T cell response in the blood as well as reduced levels of the virus in the blood and lung, indicating that they all received at least partial protection from the virus. This was all in the absence of neutralizing antibodies against the infecting strain of PRRSV.
"What this tells us is that T cells are doing the heavy lifting here," Rahe says. "And what that means is that our current vaccines are successful in helping the body identify and attack pieces of the PRRSV virus that are conserved, or that aren't mutating. If we want to produce more effective vaccines, we need to find and target those pieces on the virus itself.
"This study is an important foundational step in that direction," Rahe continues. "Hopefully we will soon be able to produce more broadly effective vaccines against PRRSV."
The work appears in Vaccine and was supported by Boehringer Ingelheim Animal Health, Inc.
Andrew Noel, a former graduate student at Iowa State University, is first author of the work. Other Iowa State University contributors include Jianqiang Zhang, Baoqing Guo, Jennifer Groeltz-Thrush, Emily Rahe and Teerawut Nedumpun. Panchan Sitthicharoenchai, assistant professor of anatomic pathology at NC State, along with Reid Phillips, Marius Kunze and Oliver Gomez-Duran of Boehringer Ingelheim Vetmedica, also contributed to the work.
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