Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A “Leaky” Vaccine with Debatable Efficacy and Safety

Abstract

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the late 1980s. Attributed to the PRRSV extensive genetic and antigenic variation and rapid mutability and evolution, nearly worldwide epidemics have been sustained by a set of emerging and re-emerging virus strains. Since the first modified live virus (MLV) vaccine was commercially available, it has been widely used for more than 20 years, for preventing and controlling PRRS. On the one hand, MLV can induce a protective immune response against homologous viruses by lightening the clinical signs of pigs and reducing the virus transmission in the affected herd, as well as helping to cost-effectively increase the production performance on pig farms affected by heterologous viruses. On the other hand, MLV can still replicate in the host, inducing viremia and virus shedding, and it fails to confer sterilizing immunity against PRRSV infection, that may accelerate viral mutation or recombination to adapt the host and to escape from the immune response, raising the risk of reversion to virulence. The unsatisfied heterologous cross-protection and safety issue of MLV are two debatable characterizations, which raise the concerns that whether it is necessary or valuable to use this leaky vaccine to protect the field viruses with a high probability of being heterologous. To provide better insights into the immune protection and safety related to MLV, recent advances and opinions on PRRSV attenuation, protection efficacy, immunosuppression, recombination, and reversion to virulence are reviewed here, hoping to give a more comprehensive recognition on MLV and to motivate scientific inspiration on novel strategies and approaches of developing the next generation of PRRS vaccine.

Simultaneous Infection With Porcine Reproductive and Respiratory Syndrome and Influenza Viruses Abrogates Clinical Protection Induced by Live Attenuated Porcine Reproductive and Respiratory Syndrome Vaccination

“…Whilst PRRS MLV vaccines can provide a significant clinical benefit, the protection against virus shedding is limited which may drive the evolution of PRRSV ( 55 , 56 ). This has been attributed to these vaccines being weakly immunogenic, especially for cellular responses ( 8 ). In line with previous reports, we confirmed that PRRS MLV vaccinated pigs recorded lower lung lesions, viraemia and viral load in lungs after a single infection with PRRSV-2, which was associated with a robust, although non-neutralizing, antibody response and a weak peripheral PRRSV-specific T cell response ( 11 , 14 , 51 , 52 ).…”

“…Both species have since spread globally, but PRRSV-1 remains predominant in Europe, while PRRSV-2 predominates in the Americas and Asia. The rapid evolution of PRRSV due to a high mutation rate when replicating its genome, and recombination between strains have resulted in substantial genetic diversity, which poses challenges for the control of PRRS by vaccination ( 8 ).…”

“…Commercially available vaccines include inactivated and live attenuated (also known as modified live virus; MLV) vaccines for both PRRSV-1 and -2 ( 9 ). Although inactivated vaccines are considered safer, MLVs are preferentially used for their higher protective efficacy ( 8 , 10 ). Studies have demonstrated an induction of a high level of PRRSV-specific antibodies which is associated with clinical protection against challenge infection with related PRRSV strains ( 9 ), but rather weak T cell responses after MLV immunization ( 11 ).…”

Simultaneous infection with porcine reproductive and respiratory syndrome and influenza viruses abrogates clinical protection induced by live attenuated porcine reproductive and respiratory syndrome vaccination

“…Whilst PRRS MLV vaccines can provide a significant clinical benefit, the protection against virus shedding is limited which may drive the evolution of PRRSV (54,55). This has been attributed to these vaccines being weakly immunogenic, especially for cellular responses (8). In line with previous reports, we confirmed that PRRS MLV vaccinated pigs recorded lower lung lesions, viraemia and viral load in lungs after a single infection with PRRSV-2, which was associated with a robust, although non-neutralizing, antibody response and a weak peripheral PRRSV-specific T cell response (11,14,50,51).…”

Evolution of pathogen tolerance and emerging infections: A missing experimental paradigm

“…In fact, the application of live vaccines might result in PRRSV variants that cause clinical severity and elevated viremia in the naïve inoculated pigs, suggesting a reversal of virulence level ( Jiang et al, 2015 ; Liu et al, 2018 ). Although mechanisms are unknown ( Zhou et al, 2021 ), tolerance after vaccination could facilitate genetic diversification of the circulating viruses, enabling them to evolve newer immune evasion strategies and revive virulence. Indeed, a recent study on chicken vaccinated against infectious bronchitis virus (IBV) has detected selection pressure, resulting in the diversification of viral coat proteins ( Franzo et al, 2019 ).…”