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Role of complement system pathways in protective immune response to treatment with heat-inactivated Mycobacterium bovis

ABSTRACT: Development of vaccines to preserve and improve human and animal health require effective protective antigens, delivery platforms and adjuvants. The immunostimulant adjuvant based on heat-inactivated Mycobacterium bovis (IV) was developed to boost protective immune response in different animal species against pathogen infection and tick infestations. To advance in vaccinology, in this study we used a serum proteomics approach with functional annotations and enrichment network analysis for the characterization of immune pathways and biomarkers associated with IV treatment in the wild boar animal model. The results support a role for IV in the activation of innate and adaptive immune responses through activation of humoral immune response, regulation of actin cytoskeleton pathway, coagulation cascade, complement system and innate immunity. A balance between different complement system pathways in response to IV activated antimicrobial responses while reducing risks for inflammatory diseases and pathogen-associated immunothrombosis. These results support a role for IV in stimulating protective immune and anti-inflammatory responses with application if different vaccine formulations.

INSTRUMENT(S):

ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Blood Serum

SUBMITTER: Margarita Villar

LAB HEAD: Margarita Villar

PROVIDER: PXD050002 | Pride | 2025-10-15

REPOSITORIES: Pride

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Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.

			Action	DRS
	JV_12-1.wiff	Wiff
	JV_12-1.wiff.scan	Wiff
	JV_12-2.wiff	Wiff
	JV_12-2.wiff.scan	Wiff
	JV_14-1.wiff	Wiff

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Role of complement system pathways in protective immune response to treatment with heat-inactivated Mycobacterium bovis

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