Despite the continuing frustrations about PRRS control, an internationally recognized veterinary virologist believes there is hope for the future in the form of a more effective vaccination strategy.

William L. Mengeling, DVM, PhD, Dipl ACVM, who retired in 2001 from the National Animal Disease Center, Ames, Iowa, discussed PRRS vaccinology in a presentation at the 2005 American Association of Swine Veterinarians Annual Meeting in Toronto.

In his AASV presentation, Mengeling proposed a new approach to PRRS vaccination that he believes could materially aid in the prevention and control of the disease. The acronym by which he identified the new approach, namely SWINE,® stands for Sensitization, Wait, Immunization, Neutralization and Eradication. He explains that the ® symbol has no meaning other than to distinguish the acronym from the more conventional use of the word swine.

“One of the advantages of the SWINE approach is that inactivated virus, attenuated virus, and virulent virus can all play a role depending on the desired result of immune stimulation -- sensitization versus immunization-- and the level of risk that can be tolerated,” says Mengeling, now a collaborative professor at Iowa State University, Ames, Iowa. “Therefore no one loses face regardless of the type of vaccine they prefer and perhaps currently recommend to others.”

Mengeling also points out that one of the major reasons that the proposed SWINE method of PRRS control is applicable today is because of “the remarkable success of genetic suppliers in keeping herds free of PRRSV and many other major pathogens of swine -- with the corollary that neonatal pigs destined to become replacement gilts are free of passively acquired antibody for such pathogens and can therefore respond to vaccine even within the first few weeks of life.”

Further, according to Mengeling, “none of the potential success of the SWINE protocol depends upon a future ‘improbable’ scientific breakthrough. All of the approaches are doable with current technologies,” he emphasizes.

Following is Mengeling’s explanation for each step in the proposed SWINE vaccination strategy to control PRRS:

Sensitization
The first step is to sensitize, or prime, the immune system to the immunogens of interest. While the focus is PRRSV, Mengeling says that other viral antigens, such as those of swine influenza virus (SIV), as well as various bacterial antigens, such as those of Escherichia coli, could also be included in an inactivated, sensitizing vaccine.

He believes that to sufficiently prime the immune system for PRRSV, at least two doses of an inactivated vaccine would be necessary. Conversely, a single dose of attenuated virus would likely be enough. But in either case it’s essential that for sensitization to be considered successful there must be clear evidence of an immune response -- as measured by humoral antibody.

Mengeling says that a starting point for the most appropriate age to give the first (or only) sensitizing dose might be 2 weeks. A second sensitizing dose, if necessary, might be administered at 6 weeks. This could change due to results of future experimentation, he emphasizes.

 

Former NADC researcher William Mengeling has proposed a new vaccination strategy using current technology and knowledge to help in the fight against PRRS.

“I presume that the most acceptable sensitizing vaccine from the standpoint of genetic suppliers would be inacti-vated,” Mengeling remarks. “In that way no additional off‑site isolation facilities would be required. It would also allow for a greater spectrum of other antigens to be included in the vaccine.”

“On the other hand, attenuated virus might be the choice of veterinarians and farm managers who choose to use fully virulent virus as the immunizing dose. However, if adequate immunity can be provided by sensitization with inactivated‑virus vaccine followed by immunization with attenuated‑virus vaccine it would be difficult to justify the ‘reloading’ of a herd with a virulent field strain of PRRSV during each round of gilt acclimatization.”

Wait
Mengeling explains that the second and very important step is to wait an appreciable interval of time between sensitization and immunization to allow maturation of the immune system relative to the immunogens being studied. “This would seem to be an especially important issue for a virus such as PRRSV that elicits a frustratingly slow developing immune response, especially in regard to the appearance of neutralizing antibody and protective immunity.”

The minimum interval for maximum effect, according to Mengeling, has yet to be determined. “But it is likely to be months rather than weeks, especially if attenuated virus, which would certainly raise a much higher antibody titer than inactivated virus, is used for sensitization and the goal is to have a low level of circulating antibody at the time the immunizing dose is administered.” Consequently, he proposes that the immunizing dose (table below) be administered as late as possible, but still soon enough to provide immunity during gestation. For example it might be administered at or about 6½ months for gilts bred at or about 8 months of age.

“The theory is that regardless of the immunogen in question, the immune response following the immunizing dose would be greater if the antibody activity previously raised by the sen-sitizing dose or doses had decreased appreciably.”

“This might be especially true for live-virus vaccines whose effectiveness depends on replication,” says Mengeling.

Immunization
The third step is to administer the immunizing dose of vaccine, Mengeling explains. “If the immunizing dose is attenuated virus, it would have been preceded by at least two sensitizing doses of inactivated virus. If the immunizing dose were virulent virus, it would have been preceded by at least one sensitizing dose of attenuated virus or at least two sensitizing doses of inactivated virus.

 

Replacement gilts free of passively acquired antibody are key in the SWINE® vaccination strategy.

“The point is that to get a sharp increase in protective immunity, the immunizing dose has to be at least one level above the sensitizing dose(s) in regard to its potential to stimulate the immune system.”

Mengeling clarifies that inclusion of virulent PRRSV as a possible “immunizing” component in the SWINE method of PRRS control is not to be construed as a recommendation for its use. It is just to make veterinarians and producers who have already committed to using fully virulent PRRSV in an attempt to induce protective immunity aware that sensitization has the potential to enhance the immune response. Moreover, prior sensitization can reduce shedding following exposure to virulent virus as well as the likelihood of untoward clinical reactions, especially when attenuated virus is used for the sensitizing dose or doses.

Mengeling notes that the terms sensitizing dose or doses and immunizing dose are defined in the context of the SWINE method of PRRS control. “A virus like SIV, in contrast to PRRSV, is so immunogenic that an appreciable level of protective immunity is likely to follow the so‑called sensitizing doses. But even for SIV it’s almost certain that immunity would be further enhanced by the subsequent administration of an immunizing dose -- which in this case would likely be another dose of inactivated‑virus vaccine.”

“And any increase of antibody activity in gilts during acclimatization would help ensure success in regard to protecting them during gestation and providing a higher protective level of antibody to their progeny via colostrum.”

 

A starting age for pigs to receive the first sensitizing dose of PRRS vaccine might be 2 weeks, and a second dose might be given at 6 weeks.

Neutralization
“The fourth step is dictated entirely by the pig’s immune response to sensitization followed by immunization,” says Mengeling. “The expectation is that the sensitization/immunization protocol is almost certain to raise a level of neutralizing antibody and protective immunity in the case of PRRSV far beyond that raised in naive gilts following more conventional vaccination procedures with either inactivated virus or attenuated virus, or following exposure to virulent virus.

“And the immune response should also be appreciably enhanced for any other pathogens for which gilts were previously sensitized and subsequently immunized.”

Eradication
The final step in the proposed SWINE method of PRRS control is to design a PRRS eradication program using the first four steps as an integral component to decrease the prevalence of infection, clinical disease and virus shedding, says Mengeling.

“The eradication effort, particularly on a herd basis, might also include other pathogens if such were included in steps one and three.”

Mengeling says that, in principle, the vaccination strategy proposed for the SWINE method of PRRS control is not much different from that used for several other pathogens. “For example, many inactivated vaccines require two doses to be effective -- the first dose to sensitize the immune system and the second to elicit an anamnestic response sufficient to provide protective immunity.”

“However, the immune response to PRRSV is unconventional in many respects. My assessment of inactivated‑ PRRSV vaccine is that even a second dose does not elicit an appreciable level of immunity. And neither repeated doses of a particular attenuated‑virus vaccine nor a particular strain of virulent virus induce markedly increased levels of antibody activity -- at least as measured by ELISA.”

“This is in contrast to the marked anamnestic responses that often follow repeated exposures to other viruses. Therefore the relative uniqueness of the SWINE method of PRRS control is the long interval between sensitization and immunization steps, and the nature of the sensitizing and immunizing doses.”

Much of the impetus for proposing the SWINE method stemmed from an unpublished study begun in 1998 and completed in 1999 at the National Animal Disease Center, says Mengeling.

Specific data of this study and several others that are pertinent to the conceptualization of the SWINE method of PRRS control are summarized in Mengeling’s AASV paper in the Proceedings of the 2005 American Association of Swine Veterinarians Annual Meeting beginning on page 289.

More research needed

The SWINE® method of PRRS control has not yet been tested directly for its merit, acknowledges William L. Mengeling, the veterinary researcher who has proposed the protocol.

“Although it seems to me so straightforward on the basis of previous studies that it can’t fail to improve on our current situation, the vagaries of PRRS and PRRSV make testing of almost any PRRS‑related idea or concept an adventure with a highly uncertain outcome.

“Moreover, the commitment of time, effort and money is extraordinary when pursuing ideas that involve pregnant gilts and their progeny. Imagine a study requiring the housing, treatment and handling of five treatment groups -- enough for adequate subsets of principals and controls of 10 gilts each, and in addition enough boars for breeding purposes.

“Then add the demand that, except for vaccination, all pigs and gilts be kept free of PRRSV and any other pathogens such as SIV that might be involved in the study, and yet in an environment that reasonably reflects on‑farm conditions -- until purposeful exposure to virulent virus -- challenge -- which in turn requires very expensive isolation facilities.”

Many other factors also would need to be considered as the research progressed, says Mengeling.

“Fortunately, the experimental testing and evaluation could be approached in a series of discreet phases,” he says. “And until initiating the final phase, a decision could be made at any point on whether to continue.”

According to Mengeling, if the study would run to completion, it would comprise, depending on the experimental group in regard to treatments at any particular phase, the following:

  • The initial phase wherein gilts would be vaccinated with either inactivated or attenuated virus (sensitizing dose or doses) -- but only after preliminary studies in regard to the best method for sensitization, including the most effective adjuvant (if inactivated vaccine were used for sensitization) and the best injection schedule in regard to both timing and number of injections.
  • A second phase wherein gilts would be vaccinated or exposed to virulent virus (immunizing dose) and tested for serologic responses.
  • A third and final phase wherein gilts would be challenged and the effect of previous treatments would be measured.

Options for vaccination strategy

Various possible permutations of the SWINE® method of PRRS control to provide enhanced protective immunity to gilts during gestation (via actively acquired antibody) and to their progeny (via passively acquired antibody).a

GILT AGEb: 2 weeks 

TYPE OF PRRSV ADMINISTEREDc

Option 1d: Inactived 

Option2: Attenuatedf   

Option 3: Inactived 

IMMUNE RESPONSEe: Sensitization

 

GILT AGEb: 6 weeks 

TYPE OF PRRSV ADMINISTEREDc

Option 1d: Inactived 

Option2: Attenuated    

Option 3: Inactived

IMMUNE RESPONSEe: Sensitization

GILT AGEb: 26 weeks      

TYPE OF PRRSV ADMINISTEREDc

Option 1d: Attenuated    

Option 2: Virulent  

Option 3: Virulent  

IMMUNE RESPONSEe: Immunization

a The possibility is that the amount of passively acquired (maternal) antibody ingested by neonatal pigs would be sufficient to provide protection at least well into the nursery phase of production.

b The assumption is that gilts would be bred at or about 8 months of age.

c The assumption is that inactivated virus would be sufficiently immunogenic so that there would be a measurable immune response (humoral antibody) after the second dose of virus. Without such, the immune system would probably not be sufficiently sensitized to respond adequately to the immunizing dose of either attenuated or virulent virus. Whether currently available inactived vaccines are sufficiently immunogenic remains in question. If not, research to improve such vaccines will be necessary.

d Assuming that option 1 would provide a satisfactory level of immunity, it would clearly be the choice for routine use because it would circumvent the repeated introduction of virulent PRRSV into the herd in question.

e As defined for the SWINE method of PRRS control.

f It is likely that a single exposure to attenuated virus would be sufficient to provide the level of sensitization required to markedly enhance the immune response to subsequent exposure to virulent virus, However, a second sensitizing dose of another strain of attenuated virus might further enhance the strength and breadth of the immune response. In North America, this could be provided, e.g., by first (at 2 weeks) administering Ingelvac PRRS MLV and subsequently (at 6 weeeks) Ingelvac PRRS ATP.

General comment: If the theorized enhanced level of maternal immunity during the first parity is proven to be a reality, futher research will be needed to determine if subsequent parities are also benefited.

Source: William Mengeling

Not much input yet on proposed vaccination method

The long-time veterinary researcher who proposed the SWINE® vaccination protocol for attempting to control PRRS says that so far, he has not had much feedback on his proposal.

“I haven’t been approached as often as I thought I would be con-sidering the difficulties we now have in controlling PRRS,” says William L. Mengeling, DVM, PhD, a career veterinary scientist and researcher with the National Animal Disease Center, who retired in 2001.

“A Spanish colleague requested approval to translate the information and submit it for publication, in a Spanish review journal, and I have been invited to summarize the same information during a lecture scheduled for a meeting in Parma, Italy, this fall.

“But I have been contacted only a few times by people in the states. What has been of interest to me is there seems to be more enthusiasm in looking for ways in which the protocol might not work than in looking at its possible benefits.”

Despite this, Mengeling says he remains convinced that the proposed vaccination protocol provides a potential answer to better immunity to PRRS. Further, he adds, “I truly believe that it -- or a permutation thereof -- will eventually be used to help control the disease. So I’m quite comfortable with the knowledge that I have done my best to present the facts as I see them and must now just wait for others with adequate resources to perhaps ‘come around’ -- at least to the point of fully testing the procedure in an unbiased manner.

“I’m also comforted by the knowledge that almost everything new I have presented in my research career has initially been questioned, so skepticism is familiar territory. But eventually many of the observations and ideas have been accepted.”