Technical Bulletin. Pfizer Animal Health. RespiSure-ONE for one-day-of-age vaccination: Assessing vaccine efficacy RSP Key Points.

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1 RSP10007 Pfizer Animal Health Technical Bulletin RespiSure-ONE for one-day-of-age vaccination: Assessing vaccine efficacy Ron D. White, DVM Pfizer Animal Health New York, NY August 2010 Key Points RespiSure-ONE (Pfizer Animal Health) has new flexible label claims that allow producers to vaccinate pigs as early as one day of age. This provides more convenience, saves time and labor costs, and benefits swine health by helping establish earlier M. hyopneumoniae immunity. In an efficacy study, pigs were vaccinated at one day of age with RespiSure-ONE, and challenged at two weeks of age with M. hyopneumoniae. 1 When compared to saline controls, vaccinates had: Significantly lower (P=0.05) lung lesion scores. Significantly lower (P=0.05) concentrations of M. hyopneumoniae in both bronchial alveolar lavage fluid and bronchial swabs collected four weeks after challenge. Significantly reduced (P=0.05) shedding in nasal swabs taken during the four-week post-challenge period. Introduction Mycoplasma hyopneumoniae remains an important pathogen in swine operations 2,3,4 and a major component of Porcine Respiratory Disease Complex (PRDC). Research has demonstrated that control of M. hyopneumoniae plays a significant role in the management of PRDC 5 and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). 6 A common bacterial pathogen, M. hyopneumoniae infects up to 80% of swine around the world in its chronic form and is characterized by high morbidity and low mortality rates. 4,7 Most pigs are infected with M. hyopneumoniae during the first three weeks of life. 8,9 In addition, research shows a positive correlation between prevalence at weaning and respiratory disease at finishing. 10 RespiSure-ONE on Day 1 Previously labeled for use in pigs seven days of age or older, RespiSure-ONE, from Pfizer Animal Health, is the only one-dose M. hyopneumoniae vaccine that can be administered to baby pigs one day of age or older. This label claim allows producers the flexibility to vaccinate baby pigs at processing or when handling pigs in the farrowing crate.

2 Vaccination early in the production cycle aids in decreasing the window of susceptibility to M. hyopneumoniae pneumonia that can result when vaccination is delayed until weaning, 11 and reduces the potential for PRRSV-induced interference with M. hyopneumoniae immunity. 6 It has been previously established that the presence of maternal antibodies does not hinder the ability of RespiSure-ONE to help protect pigs against the effects of M. hyopneumoniae challenge 25 weeks following vaccination at three to eight days of age. 12 EFFICACY FROM DAY 1 Study Design 1 The study was designed to evaluate, under controlled conditions, the efficacy of RespiSure-ONE administered at one day of age. The animal phase of this study was conducted according to the guidelines of Pfizer Animal Health s Institutional Care and Use Committee. Following vaccination and challenge, treatment group pigs were compared on the basis of: Lung lesion scores at necropsy; Prevention of M. hyopneumoniae colonization in both bronchial alveolar lavage (BAL) fluid and bronchial swab samples collected at necropsy; and, Reduction of post-challenge M. hyopneumoniae shedding in nasal swabs. Table 1 summarizes the study design. Sixty pigs from dams seronegative for M. hyopneumoniae were randomly allocated to one of two treatment groups (30 pigs per group). Pigs were vaccinated intramuscularly once at one day of age with 2 ml of saline (controls) or 2 ml of RespiSure-ONE (vaccinates). During post-vaccination observations, increased respiration was observed in two of 30 controls and in two of 30 RespiSure-ONE vaccinates. No additional post-vaccination reactions were observed. On Day 16, pigs (age 14 to 17 days) were anesthetized and challenged transtracheally with an infusion of 10 ml of a lung homogenate containing a derivative of M. hyopneumoniae strain 11. Following challenge, two RespiSure-ONE group pigs were removed from the study with a debilitating leg lameness that was not associated with M. hyopneumoniae, reducing the number of RespiSure-ONE vaccinates to 28. Assessments Nasal swabs were collected from each pig prior to challenge on Day 16 and then 7, 10, 14, 17, 21, 25, and 28 days following challenge. Swabs were submitted to the University of Minnesota Veterinary Diagnostic Laboratory for determination of the percentage of pigs shedding, M. hyopneumoniae concentrations by quantitative PCR assay, and the number of days for pigs to return to normal. The data was reported as area under the curve. At necropsy on Day 44, BAL fluid and bronchial swabs were collected for a M. hyopneumoniae quantitative PCR assay. Lungs were scored as a percentage of lung consolidation attributed to M. hyopneumoniae. 13 Investigators performing and recording clinical and/ or laboratory observations were masked to treatment assignment. Analysis A generalized linear mixed model was used to analyze data for: transformed percent total lung with lesions; transformed BAL fluid; transformed bronchial swab; transformed area under the curve; and presence/absence of M. hyopneumoniae from nasal swabs. The 5% level of significance (P 0.05) was used to assess statistical differences for all variables analyzed. IM = intramuscular 2

3 Results Lung lesions The overall mean lung consolidation score in the saline controls (7.2%) was significantly (P=0.05) higher compared to RespiSure-ONE vaccinates (0.9%) (Figure 1). The RespiSure-ONE vaccinates averaged 88% reduction in lung pathology compared to the controls. Additionally, all 30 control pigs had M. hyopneumoniae lung lesions, whereas five of 28 RespiSure-ONE vaccinates had no lesions. Figure 2 Quantitative PCR concentration of M. hyopneumoniae in BAL fluids taken at necropsy. Figure 1 Mean percent total lung consolidation by treatment. M. hyopneumoniae colonization BAL and bronchial swabs Quantitative PCR results showed that the mean concentration of M. hyopneumoniae in both BAL fluid and bronchial swab samples taken at necropsy from pigs vaccinated with RespiSure-ONE was significantly (P=0.05) lower than the concentration detected in the control pigs (Figures 2 and 3). Compared with control pigs, RespiSure-ONE vaccinates showed an 80% reduction in the number of M. hyopneumoniae bacterial cells in BAL fluid samples and an 85% reduction in bronchial swab samples. Figure 3 Quantitative PCR concentration of M. hyopneumoniae in bronchial swabs taken at necropsy. Shedding nasal swabs All nasal swabs collected prior to challenge (Study Day 16) were negative by quantitative PCR (Figure 4). At seven days after challenge, more than four times the number of control pigs shed M. hyopneumoniae as RespiSure-ONE vaccinates (16.7% vs. 3.6%); however, the difference was not significant. At 17, 21, and 24 days after challenge, the percentage of RespiSure-ONE vaccinates that shed M. hyopneumoniae was significantly (P=0.05) less than the control pigs. Additionally, the percentage of control pigs that ever shed M. hyopneumoniae was 76.7%, while only 46.4% of RespiSure-ONE vaccinates ever shed M. hyopneumoniae. 3

4 Figure 4 Percentage of pigs shedding M. hyopneumoniae as determined by quantitative PCR. Figure 5 shows the mean M. hyopneumoniae concentrations of nasal swabs. Although P values for control pigs vs. RespiSure-ONE pigs were less than 0.05 on Study Days 33 (P=0.0140), 37 (P=0.0288), 40 (P=0.0269), and 44 (P=0.0385), their contrasts were not significant since the overall test for treatment and treatment by time interaction were P= and P=0.8615, respectively. The area under the curve for M. hyopneumoniae shedding for RespiSure-ONE vaccinates (2.5 logs) was significantly (P=0.0135) less than for control pigs (4.5 logs) (Table 2). Additionally, compared with affected control pigs, affected RespiSure-ONE vaccinates returned to normal (i.e., stopped shedding M. hyopneumoniae) in significantly (P=0.05) fewer days (31.2 days vs. 6.9 days). RESEARCH IMPLICATIONS Results of this study support the label claim for RespiSure-ONE administered to pigs at one day of age. RespiSure-ONE: Helped provide safe and efficacious protection against transtracheal challenge with M. hyopneumoniae at two weeks of age. Aided in prevention of chronic pneumonia caused by M. hyopneumoniae by a significant (P=0.05) difference in lung lesion scores and 88% reduction (7.2% vs. 0.9%) in lung lesion scores compared with similarly challenged saline control pigs. Figure 5 Least squares geometric mean M. hyopneumoniae concentration by quantitative PCR. 4

5 Helped prevent colonization as shown by significantly (P=0.05) lower M. hyopneumoniae concentrations in both BAL and bronchial swabs collected four weeks after challenge. When compared with control pigs, RespiSure-ONE vaccinates showed: - 80% reduction in the number of M. hyopneumoniae cells in BAL fluid samples. - 85% reduction in bronchial swab samples. - A reduction in shedding based on lower percentage of pigs shedding and a significantly (P=0.05) smaller area under the curve from nasal swabs. CONCLUSIONS RespiSure-ONE enables swine producers to vaccinate baby pigs for M. hyopneumoniae pneumonia as early as Day 1 and offers 25-week duration of immunity when administered to pigs three to eight days of age. 11,12 It is the only vaccine labeled for: Administration to baby pigs one day of age or older. An aid in reducing severity of colonization and chronic pneumonia caused by M. hyopneumoniae. An aid in reducing shedding of M. hyopneumoniae. Vaccinating at piglet processing is convenient, saving producers time and labor costs. It also helps provide swine health benefits, such as establishing earlier immunity and reducing stress at weaning. Establishing early protective immunity is expected to help reduce sickness and death loss, and further improve the economics of production by helping reduce use of antimicrobials and costly manipulations of growing pigs. 14 Focusing control efforts on the sow herd and suckling pigs may help reduce the rate of sow-to-piglet transmission of M. hyopneumoniae in the farrowing unit, specifically in segregated production systems with all-in, all-out flow, where it is likely that colonization prior to weaning is the main source of infection. 14 Results of this study, when considered with earlier work showing the ability of RespiSure-ONE to generate duration of immunity in young pigs with or without maternal antibodies, suggest that RespiSure-ONE fills an important need in the U.S. swine industry for a safe and efficacious one-dose M. hyopneumoniae vaccine. 1,11,12,15 References 1. Data on file, Study Report No. 3127R , Pfizer Inc. 2. Harris LD, Alexander TJ. Methods of disease control. In: Straw BE, D Allaire S, Mengeling WL, Taylor DJ, eds. Diseases of Swine. 8 th ed. Ames, Iowa: Iowa State University Press; 1999: Clark LK, Schedit AB, Armstrong CH. The effect of all-in/all-out management on pigs from a herd with enzootic pneumonia. Vet Med 1991;86: Ross RF. Mycoplasmal diseases. In: Straw BE, D Allaire S, Mengeling WL, Taylor DJ, eds. Diseases of Swine. 8 th ed. Ames, Iowa: Iowa State University Press; 1999: Data on file, Study Report No. 3127R , Pfizer Inc. LSGM = least squares geometric mean a, b Values within a column with a different superscript are significantly (P 0.05) different. *Differences were not tested because the overall F-test was not significant (P=0.0635). 5

6 6. Thacker EL, Halbur PG, Thacker BJ. Effect of vaccination on dual infection with Mycoplasma hyopneumoniae and PRRSV. Proc Am Assoc Swine Pract 1999: Done S. Enzootic pneumonia (mycoplasmosis) revisited. J Pig Vet Soc 1996;38: Fano E, Pijoan C, Dee S, Deen J. Effect of Mycoplasma hyopneumoniae colonization at weaning on disease severity in growing pigs. Can J Vet Res. 2007;71: Sibila M, Nofrarias M, Lopez-Soria S, Segales J, Riera P, Llopart D, Calsamiglia M. Exploratory field study on Mycoplasma hyopneumoniae infection in suckling pigs. Vet Microbiol. 2007;121: Fano E, Pijoan C, Dee S. Mycoplasma hyopneumoniae prevalence at weaning as a predictor of the group s subsequent mycoplasma status. Proceedings Allen D. Leman Swine Conference 2005; Data on file, Study Report No. 3121C , Pfizer Inc. 12. Data on file, Study Report No. 3121C , Pfizer Inc. 13. Straw BE, D Allaire S, Mengeling WL, Taylor DJ, eds. Diseases of Swine. 8 th ed. Ames, Iowa: Iowa State University Press; 1999: Ruiz A, Utrera V, Pijoan C. Effect of Mycoplasma hyopneumoniae sow vaccination on piglet colonization at weaning. J Swine Health Prod 2003; 11: Data on file, Study Report No. 3121W , Pfizer Inc. All brands are the property of Pfizer Inc, its affiliates and/or its licensors Pfizer Inc. All rights reserved. RSP10007