Vaccines and vaccination in PRRS virus control

Introduction

The emergence of Porcine reproductive and respiratory syndrome virus in the 1980s and early 1990s was a turning point in the ways in which diseases were dealt with in pig farms. The impact of the disease, its rapid spread worldwide (by 1993 the infection was present in America, Europe and Asia) and the unusual features of the virus made evident that a vaccine was urgently needed to try to control the infection. The first vaccine commercialised was Cyblue® an inactivated vaccine produced by Cyanamid and launched in 1993 in Spain. The vaccine offered a limited protection and had the disadvantage of being produced in primary macrophage cultures. Soon afterwards (June 1994), Boehringer Ingelheim launched the first modified live vaccine against PRRSV (PRRSV2) under the name of RespPRRS (USA) and Ingelvac PRRS MLV (worldwide). Next was Porcilis PRRS (Intervet), a PRRSV1 MLV. From that point on, several MLV and inactivated vaccines have been marketed.

What can PRRS vaccines offer?

The first consideration when answering this question is that immunity against PRRSV is only partial –nonsterilizing- against heterologous strains. In practical terms, most, if not all, of the challenge situations that a pig can confront in the field are heterologous challenges. Therefore, vaccinated farms can be infected. What are then the benefits of vaccination? Firstly, vaccinated animals usually show less clinical signs and suffer less complications than unvaccinated ones. For example, abortion rates or the proportion of stillbirths are lower in vaccinated sows compared to non-vaccinated ones (Scortti et al., 2006). The protection against respiratory disease is less evident although vaccinated piglets often are less prone to suffer overt disease and bacterial complications. Secondly, vaccination reduces the duration of the viremia if infection occurs, decreasing the probability of transplacental infection and helping thus to stabilize the herd. Also, at least for PRRSV1, vaccination reduces the transmission by the horizontal route among piglets (reproduction rate below 1) (Pileri et al., 2015). Protection is thought to be mediated by both neutralizing antibodies and by cell-mediated immunity. While in most cases neutralizing antibodies are isolate-specific, there are reports indicating that broadly neutralizing antibodies, namely, antibodies capable to neutralize a vast array of strains exist (Martínez-Lobo et al., 2011, Robinson et al., 2018). How and when those broadly neutralizing antibodies are developed is not well known. It probably depends on the strain or strains with which the animal have had contact but also depends on the maturation of the immune response and the repertoire of B-cells in the individual. Regarding cell-mediated immunity, evidences also indicate that there is cross-reactivity between genetically diverse isolates although the epitopes involved have not been elucidated with precision. Unfortunately, at present it is impossible to forecast what level of protection a given vaccine can produce against a given isolate and thus, selection of one commercial brand or another cannot be done based on a prediction of its efficacy for a given farm.

Types of vaccines and vaccination schedules

At present only modified live (MLV) and inactivated PRRSV vaccines are found on the market. Primoimmunization must be done using the live virus. After exposure to the live virus, the specific immune response against the virus can be detected within 2 weeks in most animals and by day 21st after vaccination almost all animals have developed antibodies. However, neutralizing antibodies cannot be detected to significant titers until week 4 postvaccination. Even then, vaccines usually induce a relatively low neutralizing antibody response (Meier et al., 2003; Diaz et al., 2006, Madapong et al., 2017). In general, it is considered that four weeks is a reasonable period for having efficient immunity after vaccination with an MLV, even some degree of protection exist after 2-3 weeks. Inactivated vaccines are not suitable for primary immunization although if administered repeatedly immunization can be achieved (Zuckermann et al., 2007; Diaz et al., 2013). In general, inactivated vaccines are more adequate to boost humoral responses in previously immunized animals. Vaccination of primed sows before farrowing with an inactivated vaccine, boosts maternally-derived antibodies and increases the duration of colostral-derived immunity in piglets. For the acclimation of naïve gilts, the most common vaccination schedules include no less than two doses of an MLV before the first service with recall vaccination every third or fourth month. Effective duration of immunity has not been consistently demonstrated but some data suggests that the immune response starts to decrease around the fourth month after vaccination. In some instances a protocol called 6-60, namely vaccination of sows at 6 days of lactation and day 60 of gestation is also used with the aim to protect the sow in the critical late gestation phase, although no substantial benefit of this strategy has been solidly proven compared to blanket vaccination. In piglets, vaccination with an MLV has been proven to reduce viral transmission (reduction of reproduction rate) in a model where several weeks were left between vaccination and exposure. Most common protocols of vaccination of piglets are vaccination at weaning or in the maternities. Only MLV are able to induce some degree of immunity in piglets with maternally-derived antibodies although interference exist (Fablet et al., 2016, Renson et al., 2019).

Rationale use of PRRSV live vaccines

As with any other live vaccine, the use of live PRRSV vaccines requires some safety considerations. Certainly, a live vaccine works because it contains a replicating agent that induces an immune response similar to that of the wild type virus. However, in this context replication implies shedding and potential transmission of the vaccine strain. It is worth to note that replication in the piglet can be high (Martinez-Lobo et al., 2013). Actually, vaccine-derived strains are found wherever PRRS MLV are used (Murtaugh et al., 2010). Transplacental infection with vaccine strains is also possible if sows are vaccinated in late gestation. Although viremic piglets can eventually born, detrimental effects for the gestation are rarely seen. Replication and shedding of MLV are a risk factor for the generation of recombinant strains with field strains. These recombinant strains are increasingly found circulating in the field (Eclercy et al., 2019; Wang et al., 2019). Measures to minimize this undesired circumstance are based in rigorous vaccinations protocols avoiding vaccination of viremic animals. Simultaneous use of different live vaccines in the same premises (for example one for sows and a second one for piglets) should be avoided as well. Epidemiological surveillance for arising of recombinant strains having vaccine parentals is advisable.

Conclusions

PRRSV vaccines are an essential tool for the control of PRRS which benefits surpass the potential drawbacks caused by its use. Future vaccines should induce a broader and more potent immune response having little or no shedding.

Published in the proceedings of the International Pig Veterinary Society Congress – IPVS2020. For information on the event, past and future editions, check out https://ipvs2022.com/en.

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Vaccines and vaccination in PRRS virus control

References

Easy-immune® farm trial report (2)

TILMIPRO 200