Abstract:This paper aims to evaluate the efficiency of three inactive vaccines against contagious agalactia prepared with samples of Mycoplasma agalactiae isolated in Brazil and different adjuvants. Vaccine 1 adsorbed with aluminum hydroxide was administered in 23 goats (Gc1) and 13 sheep (Gov1); vaccine 2 containing Montanide IMS-2215-VG was administered in 22 goats (Gc2) and 12 sheep (Gov2) and vaccine 3, containing Montanide Gel-01 was administered in 22 goats (Gc3) and 12 sheep (Gov3). All animals were negative for… Show more
“…3,16,17 Sheep are considered prone to the development of vaccine-associated granulomas 37,40 and preclinical safety studies for sheep vaccine development usually include periodical in vivo evaluation of the reactions at the injection site over a period of a few months. 2,33 There are no reported histologic descriptions of the acute or subacute inflammatory response to vaccines. 15 Moreover, a complete pathologic characterization of vaccine-induced granulomas in sheep, including location of Al within granulomas and lymph nodes, has never been performed.…”
mentioning
confidence: 99%
“…3,16,17 Sheep are considered prone to the development of vaccine-associated granulomas 37,40 and preclinical safety studies for sheep vaccine development usually include periodical in vivo evaluation of the reactions at the injection site over a period of a few months. 2,33…”
The use of vaccines including aluminum (Al)-based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injectionsite granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P < .001) in the lymph nodes of the vaccine group (82.65 mg/g) compared with both adjuvant-only (2.53 mg/g) and control groups (0.96 mg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs.
“…3,16,17 Sheep are considered prone to the development of vaccine-associated granulomas 37,40 and preclinical safety studies for sheep vaccine development usually include periodical in vivo evaluation of the reactions at the injection site over a period of a few months. 2,33 There are no reported histologic descriptions of the acute or subacute inflammatory response to vaccines. 15 Moreover, a complete pathologic characterization of vaccine-induced granulomas in sheep, including location of Al within granulomas and lymph nodes, has never been performed.…”
mentioning
confidence: 99%
“…3,16,17 Sheep are considered prone to the development of vaccine-associated granulomas 37,40 and preclinical safety studies for sheep vaccine development usually include periodical in vivo evaluation of the reactions at the injection site over a period of a few months. 2,33…”
The use of vaccines including aluminum (Al)-based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injectionsite granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P < .001) in the lymph nodes of the vaccine group (82.65 mg/g) compared with both adjuvant-only (2.53 mg/g) and control groups (0.96 mg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs.
“…Experimental challenges with large groups, especially with lactating animals and in restricted areas, are serious limitations. Few challenge models have been described, for instance, keeping vaccinated animals in contact with animals from herds where the presence of M. agalactiae had previously been detected [ 42 ], or immersing the animals’ udders in a solution containing a bacterial culture [ 44 ], or via the intramammary [ 41 ] and nasal routes [ 45 ]. However, the absence of a smaller animal model and a dearth of specific kits to evaluate the immune responses of goats and sheep are a big hindrance and delay the development of new vaccine alternatives.…”
Section: Hurdles Challenges and Opportunities In Developing Next-gene...mentioning
Contagious agalactia (CA) is a serious multietiological disease whose classic etiological agent is Mycoplasma agalactiae and which causes high morbidity and mortality rates in infected herds. CA is classified as a notifiable disease by the World Organization for Animal Health due to its significant worldwide economic impact on livestock, primarily involving goat and sheep farms. The emergence of atypical symptoms and strains of M. agalactiae in wildlife ungulates reestablishes its highly plastic genome and is also of great epidemiological significance. Antimicrobial therapy is the main form of control, although several factors, such as intrinsic antibiotic resistance and the selection of resistant strains, must be considered. Available vaccines are few and mostly inefficient. The virulence and pathogenicity mechanisms of M. agalactiae mainly rely on surface molecules that have direct contact with the host. Because of this, they are essential for the development of vaccines. This review highlights the currently available vaccines and their limitations and the development of new vaccine possibilities, especially considering the challenge of antigenic variation and dynamic genome in this microorganism.
“…The strain included in the vaccine as well as the inactivation method and the adjuvant used are all key factors for immunogenic efficacy against potentially very variable infective strains 184–186. Mineral-oil adjuvant-inactivated vaccines induce higher and longer-lasting protective immunity than the aluminium-hydroxide-absorbed vaccines, but they can also induce lesions at the injection site 176,179,182,187. Inactivated vaccines remain sub-optimal, as most of the time they reduce clinical severity rather than preventing new infections or even milk excretion 49,180,184.…”
Section: Means and Relative Effectiveness Of Controlmentioning
Contagious agalactia (CA) is a disease caused equally by four Mycoplasma species, in single or mixed infections. Clinical signs are multiple, including mastitis, arthritis, keratoconjunctivitis, pneumonia, and septicemia, non-specific, and expressed differently depending whether sheep or goats are affected, on causative mycoplasmas as well as type of husbandry. CA has been reported worldwide and its geographic distribution maps to that of small ruminant breeding areas. However, as current diagnostic tests are expensive and difficult to implement, it is certainly underdiagnosed and prevalence data are only available for a few countries. CA control relies on vaccines, chemotherapy and good herd management practices. It requires long-term commitment but is often unsuccessful, with frequent clinical relapses. The persistence of the etiological agents, despite their overall susceptibility to antimicrobials, comes from their genetic plasticity and capacity to escape the host immune response. The existence of asymptomatic carriers and the numerous sources of infections contribute to rapid spread of the disease and complicate the control and prevention efforts. Here we review all these aspects in order to highlight recent progress made and identify gaps in knowledge or tools needed for better disease management. Discussion also underlines the detrimental effect of contagious agalactia on small ruminant welfare.
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