VANGUARD®crLyme: A next generation Lyme disease vaccine that prevents B. burgdorferi infection in dogs

Abstract

Lyme disease, a public health threat of significance to both veterinary and human medicine, is caused by the tick ( Ixodes ) transmitted spirochete, Borreliella burgdorferi . Here we report on the immunogenicity and efficacy of VANGUARD®crLyme (Zoetis), the most recent canine Lyme disease vaccine to be approved by the United States Department of Agriculture. VANGUARD®crLyme is a subunit vaccine consisting of outer surface protein A (OspA) and a recombinant outer surface protein C (OspC) based-chimeric epitope protein (chimeritope) that consists of at least 14 different linear epitopes derived from diverse OspC proteins. The combination of OspA and the OspC chimeritope (Ch14) in the vaccine formulation allows for the development of humoral immune responses that work synergistically to target spirochetes in both ticks and in mammals. Immunogenicity was assessed in purpose-bred dogs. A two-dose vaccination protocol resulted in high antibody titers to OspA and Ch14 and vaccinal antibody reacted with 25 different recombinant OspC variants. Efficacy was demonstrated using an Ixodes scapularis -purpose bred dog challenge model. Vaccination with VANGUARD®crLyme provided protection against infection and prevented the development of clinical manifestations and histopathological changes associated with Lyme disease.

The Leptospiral General Secretory Protein D (GspD), a secretin, elicits complement-independent bactericidal antibody against diverse Leptospira species and serovars

“…The sequences encoding the immunodominant and variable L5 and H5 epitopes from several Borreliella burgdorferi outer surface protein C variants were linked to form a single contiguous gene sequence. Protein expressed from this chimeritope encoding sequence, designated as Ch14, was demonstrated to elicit broadly cross reactive and protective antibodies [27] , [47] . The Ch14 chimeritope is one of two recombinant antigens that comprise the commercially successful canine Lyme disease vaccine, VANGUARD®crLyme (Zoetis) [47] , [48] .…”

“…Protein expressed from this chimeritope encoding sequence, designated as Ch14, was demonstrated to elicit broadly cross reactive and protective antibodies [27] , [47] . The Ch14 chimeritope is one of two recombinant antigens that comprise the commercially successful canine Lyme disease vaccine, VANGUARD®crLyme (Zoetis) [47] , [48] . The remarkable diversity of the Leptospira suggests that a chimeritope approach may offer a path to a broadly protective vaccine antigen for both human and veterinary leptospirosis.…”

Comparative analysis of antibody responses to outer surface protein (Osp)A and OspC in dogs vaccinated with Lyme disease vaccines

“…IgG titers to OspA and OspC were determined by ELISA using recombinant proteins as the immobilized antigens (250 ng per well; 96 well plates; 0.01 M borate buffer; overnight; 4 °C). Recombinant serotype 1 OspA, the most dominant OspA serotype in North America ( Wilske et al, 1993 ), served as the detection antigen for anti-OspA antibodies and the OspC chimeritope, Ch14 ( Marconi et al, 2020 ), served as the detection antigen for antibodies to OspC. Non-specific antibody binding was blocked by washing with blocking buffer (1% casein in PBS with 0.1% Tween 20; 300 μL per well).…”

“…Consistent with the stages of infection during which each outer surface protein is expressed, anti-OspC antibodies can target LD spirochetes infecting both ticks and mammals, whilst anti-OspA antibodies only target LD spirochetes in the tick. The combined use of OspA and OspC as vaccine antigens ( Marconi et al, 2020 ) elicits antibody responses that can target LD spirochetes during both stage of their enzootic cycle providing two independent and synergistic mechanisms of protection.…”

Controlling Lyme Disease: New Paradigms for Targeting the Tick-Pathogen-Reservoir Axis on the Horizon

“…OspC is a highly variable protein with protection only against isogenic strains in studies. The dog OspA-OspC combination vaccine uses a chimeritope that induces antibodies reacting against 25 different recombinant OspC variants ( Marconi et al, 2020 ). However, regardless of how effective a human vaccine is, it will not decrease the spread of the disease and will require a commitment to continue to vaccinate at risk individuals.…”