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Streptococcus suis autogenous vaccines: what do we know?

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In spite of decades of research on S. suis vaccines, autogenous bacterins are almost the only preventive strategy available that swine producers have access to, but which are their weak spots?

Intensification of animal food production and emergence of new production systems (such as Raised Without Antibiotics or organic systems) has resulted in emergence or re-emergence of pathogens. These new societal trends, together with the willing to reduce the use of antimicrobials in livestock productions, highlight the importance of improving existing vaccines and/or development of new vaccination strategies to fight against emerging or re-emerging pathogens.
Intensification of animal food production and emergence of new production systems (such as Raised Without Antibiotics or organic systems) has resulted in emergence or re-emergence of pathogens. These new societal trends, together with the willing to reduce the use of antimicrobials in livestock productions, highlight the importance of improving existing vaccines and/or development of new vaccination strategies to fight against emerging or re-emerging pathogens.

Streptococcus suis (S. suis) is considered one of the most important re-emerging swine bacterial agent in the era of antimicrobial restrictions. Indeed, S. suis infections are one of the main causes of antimicrobial usage in piglets, either curative or (where allowed) prophylactic/methaphylactic.

Worldwide data of S. suis antimicrobial resistance are worrisome; therefore, to reduce antimicrobial use, disease prevention should concentrate on management of predisposing factors and vaccination. Despite intensive research leading to different vaccine-candidate antigens, no universally efficacious S. suis vaccine has been commercialised so far. More research would certainly advance sub-unit vaccine development. Meantime, the only available vaccines used in the field are autogenous, which consist of killed bacteria (“bacterin”) from the predominant isolate(s) recovered in an affected farm/system, produced by licenced laboratories and given back to the same farm/system. However, there are very few scientific studies demonstrating whether the use of such vaccines in the field correlates with a reduced mortality and curative antimicrobial use. Indeed, field peer-reviewed reports on autogenous vaccines are almost non-existent - only 4 published papers in the last 30 years. In addition, controlled laboratory studies have shown contradictory results concerning protection induced by experimentally-produced bacterins (for a review see Rieckmann et al. 2020).

The unresolved issues on S. suis autogenous vaccines

1. S. suis diagnosis – at the beginning and at the end: The correct diagnosis of S. suis as a primary cause of disease may complicate the choice of the isolate(s) to be included in the autogenous vaccine. There is still an unresolved issue concerning those recovered from lungs (Obradovic et al, 2021), which are considered as secondary invaders and should probably not be included in the vaccine composition. Proper S. suis diagnosis is also important to evaluate the effectiveness of the autogenous vaccination program applied to the farm. An important confounding factor is the assessment of total mortality or total treatments instead of those directly related to clinical signs compatible with S. suis disease. It should be considered that other bacterial infections may induce similar clinical signs, such as Glaesserella (Haemophilus) parasuis. In addition, if an outbreak of an unrelated disease was present on the farm and further controlled during the vaccination trial, the improvement in health might not be directly linked to the vaccine effect. The opposite, such as a concomitant infection causing piglet mortality, might also negatively affect the evaluation of the autogenous vaccine. Therefore, confirmatory necropsy, followed by bacteriology and S. suis serotyping should be systematically performed in vaccine field studies.

2. Vaccine formulation – the secret to success: Autogenous vaccines are “manufacturer-related” as each licenced laboratory uses different protocols, antigen doses, types and concentrations of adjuvants, among other variables introduced during the manufacturing process. Adjuvants are key components of a vaccine: they have the power to modulate the vaccine efficacy, the strength and duration of the vaccine-induced immune response. Despite the importance of adjuvants, few studies have compared their effect within the same experimental trial or at least under the same conditions. A recent work comparing the effect of six different commercial adjuvants on S. suis bacterin vaccine efficacy, showed that the type of adjuvant has a paramount effect on the immune response and protection of piglets against a S. suis challenge. This study also confirmed previous findings on the limited immunogenicity and/or protection of bacterin vaccines formulated with aluminum hydroxide, commonly known as alum; while the use of oil-based adjuvant emulsions as adjuvants shows promise. Therefore, more studies are necessary on the effect of vaccine formulation.

3. Sow vaccination – the dilemma of numbers of doses. Immunization of sows might elicit protective passive maternal immunity in the progeny. Sow vaccination is less costly and labor intensive, thus representing an economical alternative to piglet vaccination. A recent field study reported that a 3-dose program in replacement gilts was required to reach a significant increase in antibody levels (Corsaut at al, 2021); providing for the first time a scientific justification for implementing such a program in external replacement gilts entering quarantine. This vaccination program resulted into a higher maternal immunity present in piglets when compared to those from non-vaccinated gilts. In another field study (Corsaut at al, 2020), sows from internal replacement, which have received a 2-dose autogenous vaccine program also showed increased levels of antibodies. However, maternal antibody transfer to piglets and thus their clinical protection at the nursery was not improved. These discrepancies might be explained by several variables, including the vaccine formulation, the use of 3 doses vs. 2 doses, and internal vs. external replacement sources among other herd-specific factors. In spite of these differences, a common feature observed between the two field studies was that duration of maternal immunity drops very fast independently of the vaccination program. This drop in maternal immunity occurs at the moment of high vulnerability of weaned piglets to S. suis infection. Therefore, the question remains on how improving the duration of maternal immunity to protect piglets during the complete nursery period.

What about a “boost dose”? This is another common practice in the field but no scientific data are available to support this prevention strategy. In one of the aforementioned studies (Corsaut at al, 2021), a “boost” vaccine dose to the originally vaccinated gilts resulted in a recall (“memory”) response in terms of antibody levels at subsequent parities. Yet, the protective effect on the progeny remains to be elucidated. Similarly, the effect of a combination of mass vaccination with repeated doses of autogenous vaccines before each parturition has not been yet scientifically studied.

4. Piglet vaccination – too young or too old: To the best of our knowledge, only three published articles have addressed the efficacy of this preventive approach in the field. In a farrow-to-finish farm, piglets received an autogenous vaccine at weaning and a booster 3 weeks after entering the nursery. The direct effect of vaccination (mortality due to S. suis) was not statistically significant. However, the calculated total and overall vaccine effectiveness (complete herd-level mortality) showed somehow potential protective effects; yet mortality due to any cause was considered here (Hopkins et al, 2019). In a field study where piglets were vaccinated at weaning and boosted 10 days later, mortality and morbidity rates in nursery pigs fluctuate regardless of treatment (Torremorell et al, 1997); confirming the difficulty in assessing the clinical outcome of vaccination and the importance of proper diagnosis. Finally, in the third study, piglets received an autogenous vaccine during the first week and at three weeks of age. This vaccination program failed to induce an antibody response and no clinical protection was observed. The lack of response may be due to interference with a high level of maternal antibodies and/or an immature immune system of very young piglets. Therefore, more research is needed to evaluate the perfect age window for piglet vaccination in order to avoid maternal interference but confer protection at the moment of S. suis clinical signs onset.

Conclusion


In spite of decades of research on S. suis vaccines, autogenous bacterins are almost the only preventive strategy available that swine producers have access to. Therefore, more field studies are essential to scientifically validate their protective effect and, consequently, their cost-benefit impact for swine producers. In addition, more experimental (laboratory) studies are required to generate scientific knowledge to improve this important preventive tool and help reducing the use of antimicrobials.

Article Comments

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04-Jul-2022 oatlands1love it , best pig app ever.
19-Jul-2022 tamas-reveszIn the referred Corsaut publication unfortunately a known low-performing Alum-adjuvanted vaccine was used, so the general conclusions regarding maternal immunity transfer and duration after autogenous sow vaccination might be misleading a bit. I have several field experiences with significant improvement in Str. suis situation (either drop of mortality or treatment rate) during nursery phase up to 10 woa in case of using spec oily adjuvanted vaccine for sows.
20-Jul-2022 marcelo.gottschHello. I will answer your comment on my name and that of my collaegue Mariela Segura (we work together on this).
1. You will find another of our papers (Corsaut L, Misener M, Canning P, Beauchamp G, Gottschalk M, Segura M. Field Study on the Immunological Response and Protective Effect of a Licensed Autogenous Vaccine to Control Streptococcus suis Infections in Post-Weaned Piglets. Vaccines (Basel). 2020 Jul 14;8(3):384.) where an oil-in-water emulsion adjuvant was used and maternal passive antibodies did not last more than 1 week of age
2. We have just finished another field study with a different autogenous vaccine (produced by another laboratory) where we observed (after 3 doses in gilts) higher level of antibodies (higher than control group...but really not that high and without killing properties as tested by the OPA test) at 3 weeks of age and for some serotypes, at 5 weeks of age.
3. I completely disagree with the concept of maternal antibodies for S. suis up to 10 weeks of age!!! S. suis is a very low immunogenic bacteria, so this is very unlikely.
4. However, we agree that different autogenous vaccines (with different adjuvants) may be different and induce different immunity...but until 10 weeks of age? again, unlikely. It would be interesting to know what test have you used to measure antibody response and with which antigen. Indeed, at 10 weeks of age, usually the natural active antibody production against S. suis-like antigens usually begins..
5. You should be very careful in the interpretation of data coming from the field without control groups...disease caused by S. suis sometimes disappears or it is reduced some time without any logical explanation...not having a control group makes the interpretation difficult
6. Just to give you an example of the latter point: in our recent study (not yet published), no antibiotic was used (nothing, zero). We did have a control group. You know what? 95% of S. suis-related diseases...were caused by Erysipelothrix rhusiopathiae...and almost no S. suis could be isolated...in a farm that had S. suis isolated from ill pigs very frequently as assessed by lab isolation. Without a control group and a complete bacteriological characterization of the isolates from diseased or dead pigs during the trial...we would have concluded that the autogenous vaccine did a great job...when the reality is that we do not know.
-I still think that sow vaccination with a very good autogenous vaccine may induce some level of protection during the very first week(s) (if you are lucky) after weaning
Thank you for your comments
regards
M. Gottschalk
21-Jul-2022 tamas-reveszThank you Marcello for the feedback! In fact, my experiences are coming from clinical evaluation of herd status before and after vaccination, nothing scientific, no measuring IgG level, etc. But I didn't even think about the long presence of MDA, only the longer impact (even after waning) of it on clinical streptococcosis, which was quite convincing, even though your argumentation regarding potential misdiagnosis is quite interesting and valid. This is a fact, that without any other changes in measurements but Str. suis sow vaccination (oily adjuvant AV), Amoxycillin usage was dropped to almost zero in the nursery period, and mortality was halved up to 10 woa. (Formerly mortality and mainly neurological clinical cases were confirmed as of Str. suis cases.)
best regards
Tamas
25-Jul-2022 calavetCan multiple vaccinations in piglets (Circovirus, Mycoplasma Hyopneumonie, Prrs) compromise an immature immune system and decrease the innate immune response, for example against Natural Killer cells?
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