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M+Pac® Mycoplasma hyopneumoniae bacterin - Technical Overview

by 5m Editor
1 July 2005, at 12:00am

By Schering-Plough Animal Health - This article provides a technical overview of Schering-Plough Animal Health's M+Pac® Mycoplasma hyopneumoniae bacterin.

Extensive Research, Optimal Efficacy and Use Flexibility Distinguish Schering-Plough Animal Health Corporation’s Popular Mycoplasma Bacterin

Doug Groth
Doug Groth
DVM, Technical Service Veterinarian
Few swine health issues rival the comprehensive economic threat posed by respiratory disease. Capable of affecting pigs of all ages, the porcine respiratory disease complex (PRDC) involves a wide variety of pathogens, etiologies and effects. Therefore, a variety of control measures must be employed with diligence to protect herds from these multifactorial attacks and preserve optimal productivity and profitability.

One of the most significant respiratory pathogens of swine is Mycoplasma hyopneumoniae, the microbe responsible for enzootic pneumonia and a major contributor to PRDC. In fact, recent survey data reveal that mycoplasmal pneumonia is the most common respiratory disease of grower/finisher pigs, reported in 68% of large U.S. production sites.1 Vaccination of herds for M. hyo has become a standard practice in many production units, thanks to the development and availability of excellent bacterins like M+Pac® and ongoing research that continues to discover new strategic ways to deploy these vaccines. Still, mycoplasmal vaccination is far from ubiquitous. Recent information on herd health practices in the U.S. reveals that only about 55% to 61% of larger producers (>2000 pig inventory) vaccinated starter/grower pigs under 70 lbs.1

Management of M. hyo represents one of the most important areas of expertise swine practitioners offer producers. The evaluation of herd serologic status, as well as identification of the appropriate vaccine protocol for a particular herd, demands a valuable combination of specialized technical knowledge and analytical skill few producers possess. Furthermore, new findings about disease progression and interactions (i.e., porcine reproductive and respiratory syndrome virus2), vaccine responses and product refinements continue to arise. This bulletin offers an overview of technical information about M+Pac, the premier M. hyo vaccine from Schering-Plough Animal Health Corporation, and summarizes recent developments relating to the role of M+Pac in effectively controlling mycoplasmal pneumonia.

Flexible Use, Powerful Emunade® Adjuvant

M+Pac provides optimal convenience and compatibility with diverse vaccination strategies due to its dosing flexibility. A conventional two-dose regimen involving two 1-mL doses (IM or SC) administered at 2-week intervals can begin as early as 1 week of age. Alternatively, a single 2-mL IM dose can be administered at 6 weeks of age or older. Either regimen provides excellent disease control efficacy and an extended duration of immunity, superior syringeability and minimal tissue reaction with a 21-day withdrawal period. Many of these benefits are the result of the powerful, dual-acting, oil-in-water Emunade adjuvant used in M+Pac. Emunade helps potentiate the antibody response generated by M+Pac while minimizing tissue irritation and enhancing flowability, even in cold temperatures.

Comparative Immune Responses and Efficacy

A multi-dimensional study was conducted at an independent lab to investigate several comprehensive aspects of M. hyo immunization.3,4 The study specifically compared the performance and effects of M+Pac (two-dose) with three competitive commercial vaccines. Fifty pigs born to sows with negative M. hyo antibody titers were randomly allotted to five treatment groups. At 3 and 5 weeks of age, one group received a 1-mL SC dose of M+Pac, while three other groups received competitive vaccines according to manufacturer’s guidelines (vaccine A: 2 mL IM; vaccine B: 2 mL IM; vaccine C: 1 mL SC). The remaining group served as controls, receiving 2 mL of saline on each vaccination day. All pigs were intratracheally challenged with an inoculum of virulent M. hyo 51 days after vaccination and were necropsied 27 days after challenge for evaluation of lung pathology. A variety of immunologic analyses were performed on blood samples obtained during the study.


Seroconversion

Serum samples collected from pigs at 45 days post-vaccination were assayed for M. hyo antibodies by ELISA (optical density 0.26 threshold for positive titer). Results shown in Figure 1 reveal that 100% of the pigs vaccinated with M+Pac seroconverted by 45 days after vaccination. Furthermore, antibody titers in M+Pac vaccinates were significantly higher (P < 0.05) than the other groups (Figure 2). M+Pac appeared to induce a stronger humoral response to vaccination.

Cell-Mediated Immunity

Acquired immunity typically involves both cell-mediated and humoral responses to antigens, and both pathways appear to be involved in M. hyo immunity. Because cell-mediated immunity (CMI) is believed to be particularly significant for controlling M. hyo infections, this study assessed CMI following vaccination with M+Pac and the other products. Lymphocyte stimulation assays were performed on blood samples, with a stimulation index (SI) =3 considered positive stimulation, an indication of the cellmediated immune response. Results summarized in Figure 3 indicate that M+Pac, as well as Vaccine A, generated significantly higher (P < 0.05) mean SI than the other groups. Again, M+Pac was distinguished from competitive products as generating a numerically more aggressive immune response in vaccinated pigs.

M. hyopneumoniae Antigen Recognition

Electrophoresis and immunoblot analyses were conducted on protein extractions performed on M. hyo cultures as well as serum samples from each of the treatment groups. A total of 31 proteins were detected in an M. hyo antigen preparation. Sera from pigs vaccinated with M+Pac recognized the greatest number of these M. hyo antigens (15 proteins; Figure 4). Of particular interest were the presence of antibodies thought to be associated with surface lipoprotein P65, which may be an important M. hyo immunogen closely linked with vaccine efficacy,5 and P97, a protein associated with bacterial adherence to respiratory tract cilia. These immunoblot results suggest that M+Pac provides a broader range of protective immunity than the other vaccines evaluated, probably because more proteins are preserved during the vaccine preparation process.

Pulmonary Protection

Regardless of immunologic distinctions, the most important element of M. hyo vaccination is disease control; specifically, protection against lung consolidation/pneumonia. Results from this study (Figure 5) indicate M+Pac vaccinates experienced the lowest numerical incidence of lung lesions and the greatest reduction (93%; P = 0.0003) compared to controls. As a result of superior antibody production, cell-mediated immune responses and antigen recognition, M+Pac provided the greatest overall protection against clinical disease.



Single-Dose Efficacy

In addition to the conventional treatment regimen involving two 1-mL doses at 2-week intervals, M+Pac has also been demonstrated to provide excellent disease prophylaxis when administered as a single 2-mL dose IM, eliminating the labor expense and animal stress associated with repeated handling. Two studies, involving either natural or artificial challenge infections, documented the efficacy of the singledose strategy.6,7 Table 1 summarizes the design and results of the studies. Lung lesion reductions ranging from 77.8% to 99.3% were observed compared to nonvaccinated controls (P = 0.013 to 0.042), verifying the efficacy of a single vaccination against both experimental and natural field challenges.

Comparative Research

The comparative efficacy of several single-dose M. hyo bacterins was the subject of a study involving seronegative pigs vaccinated at 6 weeks of age with a single 2-mL dose of either M+Pac, Ingelvac® M. hyo, or RespiSure-ONE® (plus nonvaccinated controls).8 All pigs were intratracheally challenged with virulent M. hyo inoculum 4 weeks after vaccination and necropsied 30 days later for evaluation of lung pathology. Study results compiled in Figure 6 show that pigs receiving the single M+Pac vaccination had 93.2% (P = 0.0006) less lung consolidation than control pigs and the lowest lesion incidence of any treatment group (all products significantly reduced lung lesions vs. controls in this study).

Seroconversion

Another element of this study involved monitoring of serologic status after vaccination and infection.8 Of interest was the rate of M+Pac single-dose seroconversion relative to that of pigs vaccinated with the conventional 2-dose M+Pac regimen. Blood samples were obtained from these treatment groups when vaccinated, 28 days later when challenged with M. hyo and 29 days after challenge. Results presented in Figure 7 indicate pigs vaccinated with a single M+Pac dose seroconverted at a lower rate before challenge than pigs receiving two doses, as expected. After challenge, however, both groups demonstrated high rates of seroconversion, typical of an anamnestic response after challenge. These results indicate that a single-dose M+Pac vaccination program thoroughly primed the immune system for a strong response when exposed to disease antigens.

Duration of Immunity

Because both single- and two-dose M+Pac regimens have been demonstrated to generate effective immune responses in vaccinated pigs, the duration of this immunity was the subject of additional research.

Two-Dose Duration

Pigs obtained from seronegative sows were involved in a study designed to evaluate the duration of protective immunity following M+Pac vaccination.9 At 4 weeks of age, 26 pigs were vacci-nated with 1 mL of M+Pac, with revaccination performed 2 weeks later. A second group of 28 pigs received no vaccine (nonvaccinated controls). All pigs were challenged with virulent heterologous M. hyo 4 months after the first vaccination. The pigs were euthanized 31 days after challenge and lungs were examined for gross lesions typical of M. hyo infection. Results summarized in Figure 8 show that lung consolidation resulting from the challenge infection was reduced by 93% (P = 0.0001) in the M+Pac vaccinates compared to control pigs. These results demonstrate that M+Pac vaccination provides a duration of protective immunity that extends for at least 4 months following vaccination.

Single-Dose Duration

The duration of a single M+Pac vaccination was evaluated in a study where 21 six-week-old pigs received a 2-mL IM dose and 20 nonvaccinated pigs served as in-contact controls.10 Four months after vaccination, all pigs were transtracheally challenged with a virulent M. hyo culture. The pigs were euthanized 4 weeks later so lungs could be examined for gross lesions and consolidation typical of mycoplasmal pneumonia. Blood samples were obtained monthly for serological monitoring.Lung consolidation results (Figure 9) reveal that a single 2-mL M+Pac dose reduced gross lung pathology by 86.9% (P = 0.00035) compared to controls. As expected, the single dose did not elicit a strong antibody response before challenge (Figure 10), but the vaccinates developed an anamnestic response following challenge as M+Pac primed the immune system for subsequent challenge. This study demonstrates that a single M+Pac dose protects swine from disease challenge for at least 4 months after vaccination.

Efficacy in Presence of Maternal Antibodies

In many production systems, piglets become seropositive for M. hyo antibodies as a result of colostrum ingestion from seropositive sows. The presence of these maternal antibodies is sometimes a source of confusion or concern in regard to their potential for interference with active immunization with an M. hyo vaccine. Unfortunately, maternally derived immunoglobulins may bind to vaccine antigens before a meaningful immune response is induced, rendering the vaccine ineffective. For vaccine success, maternal antibodies must decline sufficiently to allow enough unbound vaccine antigen to be properly recognized by the immune system (maternal antibody half-life is about 16 days). Therefore, the timing of vaccination in relation to maternal antibody titer is an important element for successful disease control. Two intricate studies were recently conducted to investigate the efficacy of M+Pac vaccination in pigs seropositive for maternal antibodies.

Moderate-Level Maternal Antibody Study

A study conducted under commercial production conditions evaluated the efficacy of M+Pac in piglets seropositive for maternal antibodies.11 In this study, two groups of piglets received 1 mL injections of M+Pac at either 4 or 6 weeks of age, followed by a second dose 3 weeks later. On the day of first vaccination, positive antibody mean S/P ratios of 0.92 and 0.79 were detected in the 4- and 6-week-old groups, respectively. All pigs were intratracheally challenged with virulent M. hyo at 12 weeks of age, followed by necropsy at 16 weeks for determination of lung pathology. Results of the study, summarized in Figure 11, reveal that both groups of vaccinated pigs experienced 69% less lung damage (P < 0.02) compared to nonvaccinated controls. The presence of moderate levels of maternal antibodies (S/P ratio 0.92 at vaccination) did not interfere with the ability of M+Pac to generate protective immunity.

High-Level Maternal Antibody Study

A second study was conducted to investigate the potential for higher maternal antibody levels to interfere with M+Pac vaccination.12 The study involved 79 pigs obtained from sows that had been vaccinated with an M. hyo bacterin a few weeks before farrowing, in addition to natural M. hyo exposure. The pigs were divided into five groups. Three groups of 19 pigs received a 1 mL dose of M+Pac with a second dose administered 2 weeks later. The initial doses were administered at either 1, 3 or 6 weeks of age.
Blood samples were collected at the time of initial vaccination for assessment of M. hyo serologic status. As expected, the younger pigs possessed higher levels of maternal antibody (2.62 mean S/P ratio in 1-week-old pigs), with titers falling as the pigs aged (1.42 mean S/P ratio in 6-week-old pigs). At 16 weeks of age, all pigs received an intratracheal challenge of a virulent M. hyo inoculum. Five weeks later (age 21 weeks), the pigs were necropsied and lung consolidation parameters assessed. The other two small groups of pigs served as controls (both nonvaccinated-challenged and nonvaccinated-nonchallenged controls).
Lung consolidation results are summarized in Figure 12. The 6/8-week vaccinates (with an initial mean S/P ratio of 1.42) demonstrated significant (P = 0.0026) 82% reductions in lung consolidation. This high level of maternal antibody did not interfere with the efficacy of M+Pac. However, lung consolidation in the other two groups with extremely high initial maternal antibody titers (mean S/P ratio =2.26) failed to be significantly reduced by vaccination. Because the sows in this study had experienced natural exposure as well as receiving prefarrowing M. hyo vaccination, the piglets received high levels of maternal antibodies that could be detected for as long as 12 to 15 weeks of age, but interference only lasted 6 weeks.
These study results demonstrate that maternal antibody titers as high as S/P ratio 1.42 do not interfere with M+Pac efficacy, but efficacy can be diminished by extremely high levels of maternal antibody (mean S/P ratio =2.26). Pigs do not need to be seronegative at the time of initial M+Pac vaccination to receive disease protection benefits.

Conclusions

M+Pac is a potent immunologic agent capable of helping pigs mount strong, unsurpassed immune responses to M. hyo infections. Whether administered as a conventional two-dose regimen or a convenient one-time dose, M+Pac generates a high level of immunity and an extended duration of protective immunity that significantly reduces lung pathology. Furthermore, M+Pac delivers disease protection benefits even in the presence of relatively high levels of maternal antibodies, diminishing concerns about vaccination interference. This exhaustive body of research evidence distinguishes M+Pac as the vaccine of choice for helping pork producers maintain optimal herd health and productivity.

References

1 USDA-APHIS: Veterinary Services. 2002. Part II: Reference of swine health and health management in the United States, 2000. National Animal Health Monitoring System.

2 Thacker EL, et al. Effect of vaccination on the potentiation of porcine reproductive and respiratory syndrome virus (PRRSV)-induced pneumonia by Mycoplasma hyopneumoniae. Vaccine 2000;18:1244-1252.

3 Thacker E, et al. Comparison of antibody production, lymphocyte stimulation, and protection induced by four commercial M. hyopneumoniae bacterins. Swine Health Prod 1998;6:107-112.

4 Thacker E, et al. Evaluation of the role of cell-mediated immunity and antibody in protection against pneumonia caused by M. hyopneumoniae. Proc 28th Amer Assoc Swine Practitioners 1997; Quebec City, Quebec: 149-152.

5 Kim MF, et al. Identification and mapping of an immunogenic region of Mycoplasma hyopneumoniae p65 surface lipoprotein expressed in Escherichia coli from a cloned genomic fragment. Infect Immu 1990; 58:2637-2643.

6 Data on file. Schering-Plough Animal Health Corp.

7 Rapp-Gabrielson VJ, Wasmoen TL, et al. Protection of swine vaccinated with a single dose of M. hyopneumoniae bacterin against a severe field exposure to M. hyopneumoniae. Allen D. Leman Swine Conf, 2000; Research Abstract 27 (suppl):43.

8 Groth D, et al. Evaluation of the efficacy of M+Pac in one- and two-dose regimens against competitor one-dose M. hyopneumoniae bacterins. Allen D. Leman Swine Conf Recent Research Reports, 2001; 28(suppl):41.

9 Data on file. Schering-Plough Animal Health Corp. 10 Rapp-Gabrielson V, et al. Evaluation of immunity after vaccination of swine with a single dose of M. hyopneumoniae bacterin. Proc 33rd Amer Assoc Swine Vet, 2002; Kansas City, MO:105.

11 Wasmoen T, et al. Evaluation of maternal antibody interference against active immunization of young pigs for Mycoplasma hyopneumoniae. Proc 81st Conf Res Work Animal Disease, 2000; Chicago, IL, Abstract no. 111.

12 Jayappa H, et al. Evaluation of the efficacy of M. hyopneumoniae bacterin following immunization of young pigs in the presence of varying levels of maternal antibodies. Proc 32nd Amer Assoc Swine Vet, 2001; Nashville, TN:237-241.

Further information

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