Hyogen® with ImuvantTM - Superior Protection Against Mycoplasma hyopneumoniae infection

- Single injection provides early and long lasting protection - Broad stimulation of the immune system with ImuvantTM - Trials demonstrate superior protection versus competitors - Expertise of the Ceva Lung Program




--> Some points about Enzootic Pneumonia and vaccination against Mycoplasma hyopneumoniae

--> Hyogen® with ImuvantTM

--> Conclusion



- Hyogen® with ImuvantTM
Superior Protection Against Mycoplasma hyopneumoniae infection

By Dr. Roman KREJCI, Swine Corporate Technical Manage, Ceva Animal Health



Enzootic pneumonia (EP) induced primarily by Mycoplasma hyopneumoniae cause significant economic losses in the swine industry due to the decreased growth rate, increased feed conversion ratio, and treatment expense. The overall cost of EP in the very severe forms may reach to 5.7£ per pig (Burch 2007).

There is a lot of evidence that vaccination against Mycoplasma hyopneumoniae represents an effective preventive measure reducing the impact of the disease (Maes 2008).  Vaccination does not prevent colonization of pigs by Mycoplasma hyopneumoniae when they are in contact with the infected animals; however the clinical output measured by respiratory scoring is lower in vaccinated animals. Vaccinated pigs develop less or fewer lesions in the lungs. As the consequence the lung lesion score in the slaughtered pigs is lower and this parameter is generally accepted as the indicator of the efficiency of the vaccination. Protected pigs finally prosper better and their growth is maintained.  The exact mechanisms of the prevention of the development of the disease are not yet fully understood, but both humoral and cellular immunity are considered important for control of mycoplasmal pneumonia (Thacker 2000a, Okada 2000).

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Ceva is launching the newest one shot vaccine against Mycoplasma hyopneumoniaeHyogen®. The company made it it’s goal to develop the vaccine rendering the best achievable protection against the infection in the pig farms. The innovation in Hyogen® is based on the use of the unique proprietary adjuvant ImuvantTM. This adjuvant consists of a non-toxic lipopolysaccharide (LPS) derived from the non-toxigenic Escherichia coli J5 together with a mineral oil-in-water emulsion. LPS is known to stimulate the innate immune system, which is important in the first mechanisms of defense against the infection. The interaction of the J5 LPS with the toll like receptors 4 (TLR4) in macrophages initiates the proinflammatory signaling cascade resulting in the production and secretion of cytokines and activation of other immune cells. Additionally, the TLRs signaling is also involved in the initiation of the adaptive immune response through stimulation of antigen presenting cels which produce proteins activating naïve CD4 T cells, important for the humoral immune response and antibody production.

Additionally Hyogen® contains relevant Mycoplasma hyopneumoniae lipoprotein antigens that bind to the aqueous / oil interface of the oil in the water portion of Imuvant™. This emulsion leads to enhaced antigen uptake by the antigen presenting cells. Therefore, with Imuvant™, both the innate and specific immune systems are stimulated, leading to high level of protection against Mycoplasma hyopneumoniae.

Figure 1 Scheme of the stimulation of the immune system

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The efficacy of Hyogen® with ImuvantTM was demonstrated in multiple experimental challenge model studies as well as in trials performed in the field conditions. The immune response is effectively stimulated shortly after the vaccination. Both humoral and cell-mediate immunity markers are substantially elevated already two weeks after one injection of Hyogen® (Figure 2 and 3).


Figure 2 Hummoral immune response before and after vaccination and after challenge

Figure 3 Cellular immunity (counts of IFNγ producing cells) measured 15 days post-vaccination by ELISPOT

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Immune response

As a consequence of this early and effective immune response pigs are protected against the challenge with the virulent Mycoplasma hyopneumoniae strain as early as 17 days post vaccination (Figure 4).

Figure 4 The group means of weighted lung scores of vaccinated and control animals (Herczeg 2011a).

Vaccination against Mycoplasma hyopneumoniae is recommended from the age of three weeks, which allows pigs being protected in the nursery in case of the potential early infection. Yet Mycoplasma hyopneumoniae is known to be the late colonizer, affecting mostly the fattening pigs. The immune system thus needs to be stimulated in a way that vaccinated animals are protected even when exposed to those late challenges. In the experimental challenge study Hyogen® conferred efficient protection against the infection 25 weeks after the vaccination at three weeks of age (Figure 5). Vaccinated pigs had at the time of challenge 5.2 times higher numbers of IFNγ producing cells and high titers of Mycoplasma hyopneumoniae specific antibodies which were boosted rapidly after the challenge. This documents a long immunological memory induced by Hyogen®.

Figure 5 The group means of weighted lung scores of vaccinated and control animals (Herczeg 2011b)

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The composition of in Hyogen® with ImuvantTM is the reason why pigs vaccinated with this vaccine stay healthier than if other vaccines are used, when they are exposed to the Mycoplasma hyopneumoniae infection. This was demonstrated in the comparative challenge model with two competitors Mycoplasma hyopneumoniae one shot vaccines mostly used in the current pig farms. Hyogen® conferred significantly more solid protection measured by the lung scoring (Tenk 2012).

Figure 6 Distribution of weighted lung scores post-challenge by treatment group (Box-and-whiskers graph showing median).

The impact on growth performance may be huge in pigs affected by Mycoplasma hyopneumoniae. What matters the most is then, how big is the final reduction of loss in the body weight gain in vaccinated pigs compared to non-vaccinated. In the farm condition with the presence of natural circulation of Mycoplasma hyopneumoniae, Hyogen® with ImuvantTM made the difference 34 grams per pig of the batch within the period of 11 till 24 weeks of age, when pigs were weighed (Figure 7).

Figure 7 Mean body weight gain per group between 11,5 and 24,5 weeks of age.

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Mycoplasma hyopneumoniae is the cause of a very costly disease. The prevention is possible using highly efficient vaccine. The dynamic of the infection may vary in different farms, therefore early and long lasting protection is required. Hyogen® with ImuvantTM represents the latest innovation in the prevention against EP. Through the extensive stimulation of the immune system it induces fast humoral and cell mediated response with the long-term memory. Hyogen® has proven the superior efficacy and pigs vaccinated with this vaccine gained 34 grams more than without the vaccination.

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Burch G., 2007, Cost of Disease - Enzootic Pneumonia, "Pig World" February 2007 – Octagon

Mae D. et al, 2008, Control of Mycoplasma hyopneumoniae infections in pigs, 2008, Veterinary Microbiology 126, 297-309

Thacker E. et al, 2000. Evaluation of local and systemic immune responses induced by intramuscular injection of a Mycoplasma hyopneumoniae bacterin to pigs. Am. J. Vet. Res. 61:1384–1389.

Okada M. et al, 2000, Cytological and immunological changes in bronchoalveolar lavage fuid and histological observation of lung lesions in pigs immunized with Mycoplasma hyopneumoniae inactivated vaccine prepared from broth culture supernate, 2000, Vaccine 18 (2000) 2825-2831

Herczeg J. et al., 2011, Onset of immunity after one shot of Hyogen J5® - Mycoplasma hyopneumoniae vaccine in pigs, APVS Pattaya

Herczeg J. et al, 2011, Duration of immunity after one shot of Hyogen J5®  - Mycoplasma hyopneumoniae vaccine in pigs, Proc. APVS Pattaya

Tenk M. et al., 2012, Efficacy of Hyogen vaccine in one-shot application under laboratory conditions, Proc IPVS South Korea

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