Read this article in:

PRRS Immunology

12 comments

Resolving the basis of viral and host variation will require identification and characterization of key B- and T-cell epitopes conserved among diverse PRRSV, and of the molecular and structural details of key effector antibodies, T-cell antigen receptors, and MHC molecules that mediate broad, cross-protective immunity.

The immune response to infection by type 1 and type 2 PRRSV has similar outcomes. Namely, antigen-specific humoral and cell-mediated responses are elicited, antibodies are made to a range of viral proteins, the infection is resolved, and a memory response is generated that protects against future challenge. However, the response to the two different viral genotype families is quantitatively different in important aspects. Both the severity of infection and the intensity of immune responses are reduced in type 1 PRRSV infection as compared to type 2 PRRSV infection. As a result, the study of immune protection against re-infection has been difficult in the type 1 infection model since disease can be difficult to demonstrate reproducibly, and since infection can occur without causing disease. Thus, interpretations can be misleading in the absence of solid positive and negative control with reproducible endpoints. Because of this problem, the majority of research on protective immunity and vaccinology is based on type 2 PRRSV, in which clinical disease can be reproducibly demonstrated in both respiratory and reproductive models of PRRSV infection. This limitation is relevant since type 1 PRRSV is the most important virus form in Europe, whereas PRRS in Asia and North America is caused primarily by type 2 forms.

Antibody response kinetics to type 2 PRRSV infection

Figure 1. Antibody response kinetics to type 2 PRRSV infection, showing that response to individual PRRSV proteins is the same as to an unrelated protein antigen, keyhole limpet hemocyanin (KLH) (modified from Mulupuri et al. 2008. J. Virol. 82:358-370).

The first time naive pigs are infected with PRRSV, an innate immune response occurs with evidence of interferon induction by virulent viruses, but absence of interferon by infection with low-virulent viruses. Several viral proteins block the innate interferon response but, regardless of the effectiveness of innate immunity in countering PRRSV infection, a normal humoral immune response is observed. It includes rapid production of IgM antibodies to a range of viral proteins, followed by switching to IgG antibodies to the same proteins. The kinetics of response are identical to the response to an control, noninfectious protein antigen. PRRSV-specific antibody secreting plasma cells and memory B cells are present primarily in spleen and lymphoid tissues that drain lung and reproductive tissues. Tonsil is the primary site of memory B-cells. Neutralizing antibodies appear later in infection at about the time viremia ends, and are at a low level.

Induction of memory B- and T-cells is critical for virus-specific protection against a future infection, so are essential features of protective immunity. PRRSV-specific memory cells are readily produced, and respond to individual viral proteins in cell culture. However, challenge of immune pigs does not produce a classical anamnestic response. Thus, the immune resistance status cannot be predicted by looking at serological responses following challenge. Rather, protective efficacy must be determined by virological and clinical outcomes that assess reduction or prevention of infection and disease. Challenge studies consistently show that immunity induced by live vaccines and virulent viruses induce substantial protection against future infection by unrelated viruses. The conserved antigenic epitopes that are essential for heterologous protection have not been identified.

Various immunopathological consequences of PRRSV infection, including hypergammaglobulinemia and antibody-dependent enhancement of infection, have been reported in experiments; but evidence that they occur in the field is lacking. By contrast, immunosuppressive effects of viral infection are difficult to reproduce in experiments, but there is little question in the field that overall herd health declines following a PRRS outbreak.

Effect of pig age on PRRSV growth

Figure 2. Effect of pig age on PRRSV growth. Quantitative viremia levels over time in weaned pigs and adult sows exposed to a type 2 virulent or attenuated PRRSV (adapted from Klinge et al. 2009. Virol J. 6:177-187).

Extensive variation is a hallmark of PRRS, both in the virus and in the pig’s response to the virus. Type 1 and type 2 PRRSV are genetically different, and within each group there is huge variation. Understanding the interaction of PRRSV with pigs is complicated by the fact that most research is performed with only a few virus isolates, many of which are not representative of isolates currently causing current disease. Similarly, there is tremendous variation in the response of naïve pigs to primary infection or immune pigs to field virus infection. For example, fattening pigs and adult sows have higher innate resistance to infection than do weaned pigs, although the immune response induced by infection appears to be equivalent at all ages. Resolving the basis of viral and host variation will require identification and characterization of key B- and T-cell epitopes conserved among diverse PRRSV, and of the molecular and structural details of key effector antibodies, T-cell antigen receptors, and MHC molecules that mediate broad, cross-protective immunity.

Article Comments

This area is not intended to be a place to consult authors about their articles, but rather a place for open discussion among pig333.com users.
02-Jul-2013Butch BakerButch BakerMichael,
Nice article. I do believe that in previously infected/ multiple mlv vaccinated sows there may be another immune phenomena which is anergy. In some cases mlv vaccination or prior exposure does not seem to provide cross protection in the commercial setting. It is my observation that cross protection works best when naive pigs are vaccinated prior to field virus exposure. Anyway, keep up the good science.
16-Jul-2013Michael MurtaughMichael MurtaughButch, Thank you for your insight. We certainly know best the protection afforded by exposure of naive pigs to PRRSV before challenge. And, we know for certain that immune sow herds break with PRRS. I conclude that herd immunity is more complicated than individual pig immunity, since naive sows that are vaccinated or serum exposed show solid immunity in experimental settings, and immune sows seem to be cross-resistant upon intentional challenge. Anergy might be an answer, but I am not able to exclude other possibilities. Since sow herds turn over by 40-50% per year, there must be huge variation across the herd in immune status. It would be really helpful if we could track individual sows in an immune herd that suffers a break, and see if we could match immune parameters with clinical disease. We have proposed such a study to various sponsors in the past, without success.
26-Jul-2013Butch BakerButch BakerI agree - we need to understand the dynamics of herd immunity.
25-Jul-2013 2643166945match immune parameters with clinical disease,which "the parameters",using the IDExx testing method?or test the neutralization antibody? look forward for your answer,thanks!
26-Jul-2013Michael MurtaughMichael MurtaughMany markers of response to PRRSV infection exist in the form of antibody responses to any of the viral proteins. However, the immunological correlates of protection have not yet been determined. Therefore, highly predictive indicators of clinical disease or prevention of clinical disease have not been described at this time. Neutralizing antibody, in particular, has no predictive value. In many cases of infection or vaccination that give complete or highly effective protection because there is no or insignificant induction of a neutralizing response.
26-Jul-2013Lalit BelwalLalit BelwalI would like to know correct age for vaccination in piglets from sows given live and inactivated PRRS vaccine
26-Jul-2013Michael MurtaughMichael MurtaughLalit,
As a scientist who studies anti-PRRSV immunity I do not have the training or expertise to give veterinary medical advice. Vaccine manufacturers are most likely to have the best advice for optimal use of their products. With respect to efficacy, there is a substantial body of knowledge indicating that exposure of pigs to a live PRRSV, either field virus or attenuated virus, produces an immune response the substantially protects against re-exposure to the same virus or an unrelated virus. By contrast, there is scant evidence that inactivated PRRS vaccines provide significant protection against virulent virus challenge.
30-Jul-2013Butch BakerButch BakerMy experience has been repeated vaccinations of sows with a MLV or serum inoculation to previous exposed sows (same virus) doesn't elicit a measurable immune response based on neutralizing or ELISA responses. I don't know what that means but repeated doses of the same virus yield a negative response with the mentioned antibodies. Vaccinating naive pigs is where the MLV vaccine really shines as long as it is given 30 days or more before exposure to field virus. Sometimes killed vaccine will elicit a strong booster like effect with significant antibody production but it isn't consistent and it is debatable if this provides protection from clinical signs. In the U.S. we have not found the big corrective answer to PRRSV issues.
26-Jul-2013 2643166945what is the second pic mean? the days is the vaccination days or infected the virulent days? the pig are all naive pigs?
30-Jul-2013kesheng Zhaokesheng ZhaoIs anybody studying T regular epitopes of PRRSV?
30-Jul-2013Francois MeurensFrancois MeurensNice article. Thank you.
24-Aug-2013 vaccineguruDr. Murtuagh, this is very nice article. I find very interesting the statement that virulent viruses induce interferon while low-virulent viruses do not. Could you please expand on this topic and direct me to where I can find more information on this issue.
Leave a new Comment

Access restricted to 333 users. In order to post a comment you must be logged in.

You are not subscribed to this list pig333.com in 3 minutes

Weekly newsletter with all the pig333.com updates

Log in and sign up on the list

Related products in the shop

The shop specialized in the pig sector
Advice and technical service
More than 120 brands and manufacturers
You are not subscribed to this list pig333.com in 3 minutes

Weekly newsletter with all the pig333.com updates

Log in and sign up on the list