Timing of activation of CD4+ memory cells as a possible marker to establish the efficacy of vaccines against contagious agalactia in sheep

Abstract

a b s t r a c tMycoplasma agalactiae is a major pathogen of sheep and goats in many areas of the world and particularly in Mediterranean countries. It causes contagious agalactia, an infectious disease primarily affecting mammary glands. Many vaccines against the pathogen are currently under development. The aim of the study was to investigate the involvement of T cell-mediated immunity during vaccination and challenge experiments against Mycoplasma agalactiae. A comparison of the antigen-specific expansion of interferon gamma positive T cell memory and naïve subsets was performed between vaccinated and non-vaccinated sheep to identify cellular subsets whose activation was different between protected and non-protected sheep. Data reported in this manuscript demonstrated that two out of the three vaccines used in this study protected sheep from the disease. In the protected groups CD4 + memory interferon-␥ + T cells underwent an early expansion (p < 0.05 when compared to unprotected groups), whilst memory CD8 + Interferon-␥ + T cells increased in non-protected animals 7 days after infection (p < 0.05). ␥␦ + Interferon-␥ + T cells reached peaks of expansion in infected and in two vaccinated groups thus indicating that these cells are not preferentially involved in protection or pathogenesis (p < 0.05).Hereby we propose that the early activation of CD4 + memory Interferon-␥ + T cells could be considered as a marker of protection from the disease as well as a tool to establish vaccine efficacy.

Mycoplasma agalactiae Vaccines: Current Status, Hurdles, and Opportunities Due to Advances in Pathogenicity Studies

“…Saponin-inactivated vaccines showed better results in protecting against clinical signs than those inactivated by formalin [39][40][41]. Additionally, developing an immune response with activation of T cells and IFN-gamma was correlated with developing protection against the disease [39].…”

“…Because they promote a lower immune response, vaccine formulations with different adjuvants and inactivation methods have been studied. However, it is essential to consider that the formulation potential of each immunization will depend on its intrinsic characteristics [ 39 ].…”

“…Saponin-inactivated vaccines showed better results in protecting against clinical signs than those inactivated by formalin [ 39 , 40 , 41 ]. Additionally, developing an immune response with activation of T cells and IFN-gamma was correlated with developing protection against the disease [ 39 ]. Phenol-inactivated vaccines have also been shown to be protective against CA caused by M. agalactiae [ 41 ] and M. mycoides subsp.…”

“…Amongst these, the least effective protection results were demonstrated by the inactivated commercial vaccine [ 32 ]. The saponin-inactivated vaccine and the autogenous vaccine inactivated by formalin and containing saponin demonstrated the activation of CD4 + memory Interferon-γ + T cells from the seventh day of infection to the tenth, suggesting that the timing of expansion of this subset could be considered as a correlate of protection [ 39 ].…”

“…Also associated with vaccine efficacy, microorganism excretion in body secretions is a crucial tool in determining the risk of infection spread [ 32 ]. Despite stimulating humoral and cellular responses, inactivated and attenuated vaccines present limitations due to the duration of protection [ 32 , 34 , 39 , 45 , 46 ]. Experiments indicate that different adjuvant compositions in formalin-inactivated M. agalactiae vaccines can modulate the immune response in Th1 or Th2 profiles [ 43 ].…”