Two Outer Membrane Lipoproteins from Histophilus somni Are Immunogenic in Rabbits and Sheep and Induce Protection against Bacterial Challenge in Mice

Abstract

dHistophilus somni is an economically important pathogen of cattle and other ruminants and is considered one of the key components of the bovine respiratory disease (BRD) complex, the leading cause of economic loss in the livestock industry. BRD is a multifactorial syndrome, in which a triad of agents, including bacteria, viruses, and predisposing factors or "stressors," combines to induce disease. Although vaccines against H. somni have been used for many decades, traditional bacterins have failed to demonstrate effective protection in vaccinated animals. Hence, the BRD complex continues to produce strong adverse effects on the health and well-being of stock and feeder cattle. The generation of recombinant proteins may facilitate the development of more effective vaccines against H. somni, which could confer better protection against BRD. In the present study, primers were designed to amplify, clone, express, and purify two recombinant lipoproteins from H. somni, p31 (Plp4) and p40 (LppB), which are structural proteins of the outer bacterial membrane. The results presented here demonstrate, to our knowledge for the first time, that when formulated, an experimental vaccine enriched with these two recombinant lipoproteins generates high antibody titers in rabbits and sheep and exerts a protective effect in mice against septicemia induced by H. somni bacterial challenge.

Cattle Immunized with a Recombinant Subunit Vaccine Formulation Exhibits a Trend towards Protection against Histophilus somni Bacterial Challenge

“…Current vaccines against H . somni have shown to be of limited efficacy where feedlots, ranchers and cattle producers practising proper BRD management protocols still face considerable animal losses due to systemic infections [ 5 , 22 , 23 , 49 , 50 ]. Genome-based reverse vaccinology has the advantage of identifying a larger number of vaccine candidates in a relatively short period of time [ 25 – 28 ].…”

“…OMPs) and also conserved between strains may contribute to bacterial virulence and host immunity [ 4 , 24 ]. Multiple component vaccines have the added advantage of containing more than one antigen which may increase efficacy [ 5 ].…”

“…Vaccines containing a single OMP antigen or surface fibrillar network, immunoglobulin binding protein A (IbpA) have been previously assessed by other groups [ 5 , 18 ]. For example, lipoproteins p40 (40 kDa protein) and p31 (31 kDa protein: homologous to lipoprotein Plp4 of Mannheimia haemolytica A1) when used as vaccine candidates exert a protective effect in mice against H .…”

“…Histophilus somni , previously known as Haemophilus somnus , is an economically important pathogen that affects the cattle industry by causing a variety of mucosal and systemic infections [ 1 – 5 ], including septicemia, respiratory disease, reproductive tract disorders, pericarditis, pleuritis, infectious thrombotic meningoencephalitis (ITME), myocarditis, and arthritis [ 5 – 9 ]. H .…”

“…The present day vaccines for H . somni associated disease have limited efficacy based, in part, to the strategies used by this pathogen to evade host immunity [ 5 , 20 , 21 ]. Commercial vaccines for H .…”