**8. Vaccination against** *S. aureus* **udder infection**

Mastitis is an important disease of the dairy industry that affects production and has economic losses, losses are due to high medicine cost and unusable milk which goes wasted as a result lowers producers' profit. For control of this disease it is necessary to follow some recommendations like teat sanitization, use of cloth to clean udder before and after milking, antibiotic treatment of clinically ill cases, dry cow therapy and proper management and nutrition of dairy animals [71]. In addition to these, vaccination against many pathogens is recommended for prevention and elimination of disease. One of the most important pathogenic entity in mastitis etiologies is *S. aureus*. In order to improve the general health, welfare, production as well as reproductive efficiency of dairy animals, many therapeutic as well as preventive approaches has been in use with less satisfactory results [72].

*Staphylococcus aureus* mastitis is found in many herds of dairy cows. Due to the predominant infectivity of this organism, many herds have been able to maintain a low prevalence of IMI caused by this organism. This varies greatly between herds and geographic regions, but it has been shown that calves can be infected with this pathogen during calving [73]. This pathogen usually causes only a small fraction of cases of clinical mastitis, and subclinical infections usually become chronic and refractory to treatment. The ability of this pathogen to establish a long lasting IMI varies from strain to strain. However, many toxic factors increase the viability of microorganisms in the host tissue. For longer periods of infection, fibrin deposits and abscess formation further reduce the effectiveness of the immune response. The ability of phagocytic cells to survive intracellularly affects humoral immunity and drug therapy. In addition, for example, infection with *Staphylococcus aureus*. It rarely elicits a significant innate immune response compared to *E. coli*. This avoids an acute immune response that could compromise the presence of infected tissue [74]. An effective vaccine against this pathogen must overcome some major hurdles. [1] Conservative and universal antigens are required for large variation in strains. [2] Toxic factors of "immunity", especially cell survival and the ability to not be exposed to antibodies. [3] Difficulty in assessing the effect of vaccines on reducing infections and the deleterious clinical effects of actual IMI status. The last point reflects the nature of *Staphylococcus aureus* IMI. It can be regularly excreted by bacteria in milk from infected glands. Due to L-type transformation (no cell wall mutations), *Staphylococcus aureus* can relapse in milk up to 80% of the quarter within 28 days after treatment with careful continuous sampling. IMI One or two samples are less sensitive and can correctly identify negative quarters [75].

Its need of time to control *S. aureus* for profitable business of dairy industry and for comfort of consumers with good quality milk and dairy products. In the past years, much progress was made by the researchers but in spite the use of different strategies to control mastitis, *S. aureus* is still a problem. In the dairy industry, antistaphylococcus vaccines give different results depending upon types of immunization, route of administration, adjuvant used and involvement of some other factors [76]. Considerable effort, encompassing numerous antigens, virulence factors, and bacterial strains, has been made to develop an efficacious and practical *S. aureus* vaccine.

#### **8.1 Vaccines available in market**

Many types of vaccines are in use like commercial and herd specific (autogenous) vaccines. The purpose of vaccines is to protect new infections and to stimulate cows' immune system which may provide protection against clinical mastitis [71, 77]. Vaccination may result in the increased rate of antibodies in blood circulation against *S. aureus* pathogens which decreased bacterial growth rate after entering into the udder. The resulting increased immunity may decrease pathogen damage to milk producing tissues, decreased inflammation, and enhance tissue repair. Commercial preparations of vaccine against mastitis caused by *S. aureus* are available in the market [54]. Currently there are only 2 commercially available vaccines are in use for bovine mastitis control. Lysigin® is available in the United States and Starvac® (hipra) is available in Europe and Canada. Many others are in trials and local practices with no wide range application [6].

#### *8.1.1 Lysigin®*

Bacteria containing lysed polyvalent phage-type cultures (including several types of capsular sera) are commercially available in the United States (Lysigin; Boehringer Ingelheim, Ridgefield, CT, USA). This product was derived from a Louisiana study conducted twice every 6 months at 2-week intervals for coagulase-negative staphylococcus (CNS) and *Staphylococcus aureus* calves with decreased IMI. However, the problem that arose was that infection studies showed that this bacteriocin did not prevent IMI, did not increase IMI clearance, and did not affect SCC or post-exposure lactation. The clinical score in heifers treated with Lysigin improved and the clinical course of mastitis was short. Immunization with Lysigin increased the level of bovine serum against *Staphylococcus aureus* IgG1, but did not affect the concentration of IgG1, IgG2 or IgM in milk [75].

Lysigin® is a multivalent vaccine which is prepared by using the mastitis causing strains of *S. aureus*, disintegrated into smaller particles. Early studies showed that this vaccine reduces the risk of new infections, lowers somatic cell count and thus lowers clinical mastitis effects. It is evident from experimental studies that by following a proper vaccination schedule early in life of heifer staphylococcal mastitis can be avoided. Moreover, in some recent studies animals in which this vaccine was administered showed clinical symptoms of mastitis. But these animals recovered earlier than non-vaccinated animals; also, there was no difference in somatic cell count and *anti-S. aureus* antibodies. So, this vaccine failed to provide sufficient antibodies in milk to help leukocytes in the elimination of *S. aureus* bacteria from mammary glands. But Lysigin® vaccinated animals have a higher cure rate as compared to other animals [6, 78].

#### *8.1.2 Starvac®*

It's a multivalent vaccine which is mixture of inactivated *E. coli* and inactivated *S. aureus* which shows SAAC (slime associated antigenic complex). This preparation helps reduce clinical mastitis cases to some extent that are caused by *S. aureus* and *E. coli* bacteria. This vaccine increases antibodies but does not provide complete protection from mastitis, but decreases intramammary infections and also decreases rate of transfer of infections [79, 80].
