The aim of this study was to evaluate vaccine efficacy of a commercial vaccine (Startvac, Hipra Spain) aimed at reducing intramammary infections (IMI) with Staphylococcus aureus and coagulase-negative staphylococci under field conditions. During the 21-mo duration of the study, 1,156 lactations from 809 cows were enrolled in 2 herds. During the first phase of the trial, all cows that were due to calve were vaccinated until approximately 50% of cows in the milking herd were vaccinated (at ~6mo). At that point, when 50% vaccination coverage was reached, cows that were due to calve were randomly assigned to be vaccinated or left as negative controls. Cure rate, rate of new infection, prevalence, and duration of infections were analyzed. Vaccination resulted in a moderate reduction in incidence of new staphylococcal IMI and a more pronounced reduction in duration of IMI associated with reduction of the basic reproduction ratio of Staph. aureus by approximately 45% and of coagulase-negative staphylococci by approximately 35%. The utilization of vaccine in combination with other infection-control procedures, such as excellent milking procedures, treatment, segregation, and culling of known infected cattle, will result in an important reduction in incidence and duration of intramammary staphylococcal infections.

No abstract

No abstract

An experimental trial was conducted to explore the effect of vaccination with a polyvalent vaccine against mastitis (Startvac) on the early immune response after experimental intramammary challenge with a heterologous killed Staphylococcus aureus strain. The effect of vaccination on milk production, clinical signs, quarter milk somatic cell count, milk polymorphonuclear neutrophilic leukocyte (PMN) concentration and viability, the concentration of antigen-specific antibodies [slime associated antigenic complex (SAAC) and J5] and their IgG1 and IgG2 subtypes in both serum and whey, and the antigen-specific IFN-γ, IL-4, and IL-17 production by blood lymphocytes after in vitro stimulation with S. aureus and Escherichia coli extracts were determined. A cohort of 8 clinically healthy end-term cows and heifers were conveniently selected, of which half was vaccinated with Startvac at 45 and 10 d before the expected calving date and half served as nonvaccinated control animals. At 15 d in milk, 2 contralateral quarters of each of the 8 animals were challenged with 2×10 cfu/mL of the formaldehyde-killed S. aureusC195strain. The 2 other quarters were infused with phosphate-buffered saline and served as control quarters. The increase in both quarter milk somatic cell count and PMN concentration and the drop in milk production after S. aureus inoculation was less pronounced in the vaccinates than in the nonvaccinates, reflecting a less severe inflammatory response. No significant differences in PMN viability between vaccinates and nonvaccinates could be demonstrated. The serum SAAC- and J5-specific antibody concentration significantly increased across the dry period in the vaccinated animals only. The whey concentration of SAAC-specific antibodies was significantly higher in vaccinates than in nonvaccinates at both 15 and 17 d in milk, independent from the challenge status of the quarters. No significant differences in the whey J5-specific antibody concentration were observed. Vaccination with Startvac seems to primarily evoke a Th2 response for S. aureus characterized by a shift toward the IgG1 antibody subtype and accompanied by a less pronounced Th1 response. The type of response against E. coli was less clear, though a weak but significant shift toward the IgG2 antibody subtype after vaccination and high IFN-γ levels after in vitro stimulation suggest a Th1 response. The increased SAAC-specific antibody concentration in whey in vaccinates compared with nonvaccinates most probably triggers the opsonization of the inoculated S. aureus bacteria, resulting in a more efficient elimination of the bacteria from the mammary gland.

Since the genetic sequence of SARS-CoV-2 became available in January 2020, new vaccines have been developed at an unprecedented speed. The current vaccines have been directly associated with a decline in new infection rates, prevention of severe disease and an outstanding decrease in mortality rates. However, the pandemic is still far from being over. New Variants of Concern (VoCs) are continuously evolving. Thus, it is essential to develop accessible second-generation COVID-19 vaccines against known and future VoCs to mitigate the current pandemic. Here, we provide preclinical data showing the immunogenicity, efficacy, and safety results in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine candidate (PHH-1V) which consists of a novel RBD fusion heterodimer containing the B.1.1.7 (alpha) and B.1.351 (beta) variants of SARS-CoV-2, formulated with an oil-based adjuvant equivalent to MF59C.1. BALB/c and K18-hACE2 mice were immunized with different doses of recombinant RBD fusion heterodimer, following a two-dose prime-and-boost schedule. Upon 20 μg RBD fusion heterodimer/dose immunization, BALB/c mice produced RBD-binding antibodies with neutralising activity against the alpha, beta, gamma, and delta variants. Furthermore, vaccination elicited robust activation of CD4+ and CD8+ T cells with early expression of Th1 cytokines upon in vitro restimulation, along with a good tolerability profile. Importantly, vaccination with 10 μg or 20 μg RBD fusion heterodimer/dose conferred 100% efficacy preventing mortality and bodyweight loss upon SARS-CoV-2 challenge in K18-hACE2 mice. These findings demonstrate the feasibility of this novel recombinant vaccine strategy, allowing the inclusion of up to 2 different RBD proteins in the same vaccine. Most importantly, this new platform is easy to adapt to future VoCs and has a good stability profile, thus ensuring its global distribution.