Vaccine updates for important swine Mycoplasmas

Assignment

on

DIVISION OF BACTERIOLOGY AND MYCOLOGY, IVRI

Mamta singh

Phd Scholar

Roll no. 1773

Swine mycoplasma• M .hyopneomoniae-enzootic pneumonia• M .hyosynoviae-arthritis• M .hyorhinis- mainly commensels, rhinitisVaccines –M .hyosynoviae-no commercial vaccine

A vaccine specific for M. hyosynoviae was investigated in Denmark and induced a high level of specific serum IgG in all animals one week post booster (Lauritsen, K. T. et al. 2010)

• M .hyorhinis-no commercial vaccine• M .hyopneomoniae

commercially available vaccinesExperimental vaccines

Whole-cell bacterins• major advantages of M. hyopneumoniae vaccination include improvement of daily

weight gain(2–8%) and feed conversion ratio (2–5%), shorter time to reach slaughter weight, reduced clinical signs, lung lesions and less treatment costs (Maes et al., 1999)

• Despite the beneficial effects, bacterins provide only partial protection,do not prevent colonization of M. hyopneumoniae on the epithelial cells (Thacker et al., 2000)

• vaccination is still considered the most effective practice for controlling this infection (Mateusen et al., 2002)

• commercially available M. hyopneumoniae vaccines are made from killed mycoplasma cultures (bacterins) but have different adjuvants ,mild like aluminum salts, whereas the oil-based ones, usually in the form of emulsions (oil and water mix) are more reactive and may take a longer time to be taken up, giving a more prolonged release and stimulation (Yuki and Kiyono, 2003)

• Vaccination with inactivated, adjuvanted whole-cell bacterins (alone or in combination with antibiotics) is frequently used worldwide to control M. hyopneumoniae infections (Haesebrouck et al., 2004)

Continued….

• efficacy of vaccination has been variable, may result from different factors like infection level, age of infection, complicating factors and variability between different isolates of M. hyopneumoniae (Calus et al., 2007; Villarreal et al., 2011)

• studies indicate that currently available commercial vaccines can reduce the number of organisms in the respiratory tract (Meyns et al., 2006; Villarreal et al., 2011), and consequently, the level of infection in the animals, and by extension likely also in the herd (Sibila et al., 2007)

• vaccination significantly reduces clinical symptoms and lung lesions, only limited reduction occurs in transmission of M. hyopneumoniae (Meyns et al., 2006; Villarreal et al., 2011)

• current commercial vaccines are mostly based on the J strain, which was originally isolated from a pig herd in the UK, therefore be questioned whether this strain has similar characteristics as the M. hyopneumoniae strains circulating in pig herds in other parts of the world (Stakenborg et al., 2005; Vranckx et al., 2011)

• maternal antibodies interference a single dose of M. hyopneumoniae bacterin to pigs approximately 1 week of age induced long-lasting protective immunity, with reduction in the extent of lung lesions after challenge with a virulent strain of M. hyopneumoniae (Reynolds et al., 2009)

Circumvent PCV M- merck intervetCircovirus and Mycoplasma combination swine vaccine(porcine circovirus vaccine, type 2, mycoplasma hyopneumoniae bacterin, adjuvanted with Microsol Diluvac Forte® Killed Baculovirus Vector)• in healthy swine 3 weeks of age or older as an aid in the prevention of viremia, as an aid in the reduction of virus shedding caused by Porcine Circovirus Type 2, and as an aid in the control of pneumonia caused by Mycoplasma hyopneumoniae. •Dosage: 2 ml IM, repeat in 3 weeks. 21 day slaughter withdrawal•ready-to-use combination vaccine * Provides maximum performance and less variation in finishing

Ingelvac MycoFLEX- inglovacHighly syringeable bacterin recommended for the vaccination of healthy, susceptible swine 3 wks of age or older as an aid in the reduction of enzootic Pneumonia caused by Mycoplasma hyopneumoniaeDosage: 1 ml IM. Duration of immunity is at least 26 wks. Semi-annual revaccination is recommended for breeding swine. 21 day slaughter withdrawal

Circumvent PCV-M G2 swine vaccine- merck intervet -for use in healthy swine as an aid in the prevention of viremia, as an aid in the reduction of virus shedding, as an aid in the reduction of lymphoid infection caused by Porcine Circovirus Type 2 (PCV2), and as an aid in the reduction of lung lesions due to Mycoplasma hyopneumoniae. Demonstrated PCV2 efficacy for at least 20 weeks following completion of vaccination Dosage:Option 1 - single 2 ml dose IM for pigs 3 weeks of age or older.Option 2 - 1 ml IM for pigs as early as 3 days of age, repeat in 3 weeks.21 day slaughter withdrawal• only PCV2 vaccine with one- or two-dose options that can be administered as early as 3 days of age* Long, strong 5-month duration of immunity lasts 25% longer than the competition* Ready-to-use combination vaccine for Circovirus and M. hyopneumoniae...no mixing, combining or risk of contamination from vaccination process

M+PAC –Intervet Schering-Plough- Recommended for use as an aid in the prevention ofPneumonia caused by Mycoplasma hyopneumoniae infection in swine. Dosage: 1 ml IM or subcut to pigs 7-10 days of age, repeat in 14 days. For herds that use a single-dose program, vaccinate pigs at 6 wks of age or older with a single 2 ml IM dose. 21 day slaughter withdrawal

RespiSure – zoetis -Highly antigenic whole cell inactivated Mycoplasma hyopneumoniae bacterin. Adjuvanted with an oil adjuvent, Amphigen to enhance and prolong the immune response without causing detectable tissue damage at injection site. Dosage: Shake well and inject IM. Pigs - 2 ml at 1 wk, repeat in 2 wks; Sows - 2 ml at 6 wks and 2 wks prior to farrowing. Revaccinate annually. 21 day slaughter withdrawal

RespiSure One – zoetis For vaccination of healthy swine 1 day of age or older as an aid in preventing chronic Pneumonia caused by Mycoplasma hyopneumoniae. Dosage: 2 ml IM. Semi-annual revaccination with a single dose of Respi Sure One is recommended. 21 day slaughter withdrawal * More convenient, more flexibility* Vaccinate pigs as early as one day of age* One-dose Mycoplasma vaccine

RespiSure-One ER Bac Plus – zoetis - For vaccination of healthy swine 3 wks or older as an aid in preventing disease caused by Erysipelas rhusiopathiae for a period of 20 wks, and Mycoplasma hyopneumoniae for a period of 23 wks•Dosage: 2 ml IM, revaccinate with erysipelas bacterin in 3 wks. Revaccinate semi-annually. 21 day slaughter withdrawal

Suvaxyn RespiFend MH/HPS- zoetis - vaccination of healthy swine for prevention of clinical signs, disease and death due to porcine Polyserositis & Arthritis disease (Glasser's disease) associated with Haemophilus parauis serovars 4 & 5, and as an aid in the prevention of respiratory disease associated with Mycoplasma hyopneumoniae•Dosage: Baby pigs - 2 ml IM at 7-10 days of age, repeat in 2-3 wks; Feeder pigs - 2 ml IM at time of arrival, repeat at 2-3 wks; Breeding stock - two 2 ml IM doses 2-3 wks apart prior to introduction to herd. 21 day slaughter withdrawal• Anaphylactic reactions may occur

New and experimental vaccines

• Whole cell vaccines also have high production costs because of the difficulty of cultivating M. hyopneumoniae in vitro (Kobisch and Friis, 1996)

• Recombinant DNA technology can be used to overcome problems encountered with conventional vaccines

• However, Mycoplasma sp. uses an unusual genetic code. The amino acid tryptophan is not encoded by TGG, as in most organisms, but by TGA, which is a stop codon (Razin et al., 1998)

• difference has hampered the expression of genes of M. hyopneumoniae containing TGA codons in Escherichia coli, the most attractive system used for production of recombinant proteins (Nuc and Nuc, 2006)

• Simionatto et al. (2009) described optimization of a PCR protocol for site directed mutation of TGA codons to replace TGA codons with TGG in 14 genes from M. hyopneumoniae, allowing the cloning and expression of these genes in E. coli

Recombinant subunit and recombinant vector vaccine• adhesin P97 protein, identified as an important adhesion of M.

hyopneumoniae (Zhang et al., 1995) has been the most studied and best defined potential protective antigen against M. hyopneumoniae

• King et al. (1997) reported that a subunit vaccine based on recombinant adhesin P97 did not induce significant protection in challenged pigs, However, when the C-terminal region of P97 (R1) was fused to Pseudomonas toxin A, immunized mice and pigs produced specific immune responses against R1 (Chen et al., 2001)

• Oral vaccination with recombinant E. rhusiopathiae strains expressing the P97 protein reduced the severity of pneumonic lung lesions caused by M. hyopneumoniae infection, showing that E. rhusiopathiae may be a promising vaccine vector for delivering foreign antigens to the immune systems of pigs (Ogawa et al., 2009)

Recombinant vector vaccine• Mucosal adjuvants and intranasal vaccine delivery have received special

attention as alternatives that may increase the mucosal immunity

• Conceicao et al. (2006) have reported that a recombinant subunit vaccine containing the R1 subunit of P97 fused to the B subunit of thermolabile enterotoxin of E. coli, a parenteral and mucosal adjuvant (rLTBR1) induced systemic and mucosal antibodies against R1 in mice

• Shimoji et al. (2003) reported that a YS-19 attenuated strain of Erysipelothrix rhusiopathiae expressing the R1 region of P97 was able to reduce lung lesions in intranasally (IN) immunized pigs when they were challenged but havig no humoral or cell-mediated immune response

• Okamba et al. (2007) showed that mice immunized IN with defective adenovirus expressing the C-terminal region of P97 (rAdP97c) induced a systemic Th1/Th2 immune response and local immunity ,However bacterin-based commercial vaccine was more effective in inducing protective immunity (Okamba et al., 2010)

Recombinant vector vaccine

• Mice immunized orally with Salmonella typhimurium aroA CS332 harboring the R1 region of P97 (Chen et al., 2006a) and the R2 subunit of ribonucleotide reductase (NrdF) of M. hyopneumoniae (Chen et al., 2006b) showed a Th1-based immune response, but no humoral or mucosal immune responses

• However, when the NrdF R2 subunit was expressed in S. typhimurium aroASL3261, a mucosal immune response was observed in mice (Fagan et al., 1997)

DNA Vaccines• Significant immune responses have been observed in response to

DNA vaccines based on heat shock protein P42

• beside induction of both Th1 and Th2 immune responses in mice , antiserum from the immunized animals was found to inhibit the growth of M. hyopneumoniae (Chen et al., 2003)

• Similar results were described using a DNA vaccine with the antigen P46, Both Th1 and Th2 immune responses were obtained in mice, with an increase in the IFN-g level (Galli et al., 2012)

• DNA vaccines might represent a promising strategy for developing more effective vaccines against EP. Despite the immunizing properties of these antigens and the reduced severity of lung lesions, none of them is currently able to offer total protection or a similar protection as the commercial vaccines

Multivalent vaccines• Multivalent formulations , another alternative in offering better protection

against M. hyopneumoniae (Chen et al., 2008)

• Five recombinant antigens of M. hyopneumoniae (P97, P97R1, NRDF, P36, and P46) were evaluated as DNA and protein vaccines

• analysis of mice immunized with the cocktail of antigens administered as DNA vaccine revealed that only P97 and P36 induced IgG in the serum

• Intramuscular immunization with a cocktail of antigens (P97, P97R1, NRDF, P36, and P46) as a DNA vaccine induced a Th1 immune response, while antibody responses appeared to be antigen dependent

• Subcutaneous immunization with the same cocktail administered as a recombinant subunit vaccine induced humoral and Th1 immune responses

• combination DNA and subunit vaccine was used, both humoral and Th1 responses were obtained

Conclusion and future perspectives• current measures do not provide sustainable control of the

disease, although they are beneficial from an economic point of view

• Commercial vaccines are used to limit M. hyopneumoniae infection, however little is known about the exact mechanisms of protection

• Efforts to develop a more effective vaccine against mycoplasmas have been proposed and vaccines developed using recombinant DNA technology represents a viable alternative

• Furthermore, it is clear that investigations into the host immune response are required in order to understand the role it plays, both in protection and in the induction of lesion

Thank you