Mastitis vaccines to reduce antibiotic use

Mastitis continues to be the disease that causes the most economic losses in dairy cattle and the one that generates the greatest use of antibiotics on dairy farms.

The objective of vaccination against mastitis is to stimulate the cow’s immune system, to protect it from new intramammary infections (IIM). For example, vaccination can increase circulating antibodies against mastitis pathogens, to prevent or limit bacterial development in the mammary gland. By improving immunity, damage to milk-producing tissues is minimized, modifying the inflammatory response, promoting tissue repair and reducing the clinical expression of the disease.

Combined vaccines against S. aureus and Escherichia coli

Vaccines against mastitis are mainly directed against Staphylococcus aureus and Escherichia coli. However, there are multipurpose vaccines that combine protection against both pathogens in a single vaccine. The Startvac vaccine (Hipra), which was launched on the market in 2009, acts against both pathogens and to date numerous works have been published on its effectiveness worldwide. During the multiplication of coliforms, the Startvac vaccine with the active ingredient of Escherichia coli J5 generates antibodies that recognize the bacteria and it is digested. In the case of Staphylococcus aureus, they can generate “biofilm” which is a mucous layer that surrounds and protects the bacteria, generating resistance to antibiotics and chronicity (Pedersen et al., 2021).

The Startvac vaccine prevents the development of biofilm and prevents new IIMs. The overall effect of the vaccine increases the number of healthy cows, reduces the culling rate and the use of antibiotics and increases milk production. Startvac vaccine is indicated to reduce the incidence of subclinical mastitis and the severity of clinical signs of clinical mastitis caused by Staphylococcus aureus, coliforms and coagulase-negative staphylococci. 3 doses are administered: First injection 60 days before the expected date of delivery. Second injection 30 days before delivery. Third injection between 40-50 days postpartum. The complete schedule induces immunity from approximately day 13 after the first injection, until approximately day 78 after the third injection (equivalent to 130 days after delivery).

The complete immunization program must be repeated in each pregnancy. An alternative protocol was tested by Bradley et al. (2015) in a trial explained below, where a massive or savanna application was carried out, in which all animals are revaccinated every 3 months, regardless of their physiological stage (lactation, dry and non-lactation pregnant heifers). This type of protocol protects the animals at all times and even generates herd immunity, which can be very useful in the control of Staphylococcus aureus and coagulase-negative staphylococci.

Startvac Vaccine Studies

Schukken et al. (2014) reported that the Startvac vaccine reduced the duration of IIM due to Staphylococcus aureus, due to the reduction in the reproduction rate by 45%, compared to unvaccinated cows.

Bradley et al. (2015) reported that cows vaccinated with Startvac had a significant reduction in the severity of clinical cases due to coliforms, compared to unvaccinated cows. Vaccinated cows produced almost 2 liters more per day during the first 120 days of lactation (See Figure 1), compared to unvaccinated cows. The return on investment was 2.57 to 1.

Kenzaki et al. (2018) demonstrated the effectiveness of the Startvac vaccine in a dairy farm with klebsiella spp. The incidence of clinical mastitis decreased from 2016 (59.1%) to 2017 (24.5%) by 58.54%. See figure 2. In addition, the cows annually produced almost 1 liter more milk per day. The return on investment was 2.69 to 1. The production of specific antibodies against lipopolysaccharide core antigens, which are common to all Gram-negative bacteria, allows not only their action against Escherichia coli, but also against Klebsiella spp.

Vaccine against Streptococcus uberis

Streptococcus uberis is one of the main environmental pathogens, but there are strains with contagious behavior. There are IIMs with low cure rates and it is necessary in these cases to perform extended antibiotic therapy to avoid recurrences. Due to the global trend towards reduction in the use of antibiotics, other strategies are necessary to combat this pathogen. Among them, we find tools that increase the resistance of animals to combat the infection and this can be achieved through specific immunity against Streptococcus uberis; through vaccination.

The Ubac (Hipra) vaccine was launched on the market in 2018 and has some differences from Startvac in terms of technology. Firstly, it is a subunit vaccine, that is, not the entire Streptococcus uberis was used as an antigen, but only a fraction of its cell wall called BAC, which is the adhesion component of the biofilm. In addition, it includes an immunostimulant which is lipoteichoic acid. It is indicated to reduce the incidence of clinical mastitis, the somatic cell count (SCC) and the loss in milk production caused by Streptococcus uberis. 3 doses are administered: First injection 60 days before the expected date of delivery. Second injection 21 days before the expected delivery date. Third injection 15 days postpartum.

The complete scheme induces immunity from approximately day 36 after the second injection, until approximately the first 5 months of lactation. The complete immunization program must be repeated in each pregnancy. Beulens et al. (2021) used a masal or savannah protocol, with 3 doses of primary vaccination, with intervals between them of 5 weeks and then a revaccination every 6 months, regardless of their physiological stage (lactation, dry and non-lactation pregnant heifers). This protocol has the benefit of obtaining faster results, since all animals are vaccinated at the same time.

Ubac Vaccine Studies

Puig et al. (2018) reported that cows vaccinated with Ubac reduced the incidence of clinical mastitis due to Streptococcus uberis by 52.53% (See Figure 3) and the use of antibiotics by 56%, compared to unvaccinated cows. Animals with subclinical IIM due to Streptococcus uberis produced 3 liters more per day, compared to unvaccinated animals. See figure 4.

Collado et al. (2018) determined that the Hipramune U adjuvant of the Ubac vaccine induces high levels of antibodies that inhibit biofilm formation and act against strains of Streptococcus uberis of different geographical origin and ability to form biofilm. They also reported a significant reduction in the bacterial count of Streptococcus uberis and SCC in vaccinated heifers, increasing the cure rate of infected quarters.

Beulens et al. (2021) demonstrated that cows vaccinated with Ubac reduced the incidence of clinical mastitis due to Streptococcus uberis by 40% and the use of antibiotics by 44%, compared to unvaccinated cows. The number of animals with a SCC > 100,000 cells/ml and a subclinical IIM due to Streptococcus uberis, was reduced by 50% after 6 months, compared to the unvaccinated.

Baratelli et al. 2018, reported that the simultaneous administration of Startvac and Ubac did not produce adverse reactions.

Conclusions

Worldwide work demonstrated that the Startvac and Ubac vaccines reduced new IIM (subclinical mastitis) and the incidence of clinical mastitis (reduction in the use of antibiotics and milk discard), increased the cure rate, reduced the severity and duration of infection, cow culling and SCC decreased and milk production increased.

Startvac is being marketed in more than 66 countries, with more than 25 million animals vaccinated.

In addition, Hipra provides a free PCR diagnostic service through Uddercheck to determine the prevalence of mastitis pathogens in tank milk and cows with clinical mastitis. It has been validated in 22 European countries, with 8,000 samples in 4,000 dairy farms.

Vaccination against mastitis is an important tool to incorporate into a mastitis prevention program, combined with disease prevention and control measures.

Dr. Eial Izak – Mastitis and Milk Quality Consultant

Figure 1. Milk production per day in the first 120 days of lactation in cows vaccinated and not vaccinated with Startvac.

Figure 2. Annual reduction of the Startvac vaccine in incidence of mastitis due to Klebsiella spp., deaths and discarding.

Figure 3. Incidence of clinical mastitis due to Streptococcus uberis in cows vaccinated with UBAC and unvaccinated (Placebo).

Figure 4. Daily milk production between animals vaccinated with UBAC and unvaccinated (placebo) with subclinical infections by Streptococcus uberis. *Significant differences.

 
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