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Delineating surface epitopes of lyme disease pathogen targeted by highly protective antibodies of New Zealand white rabbits

Rogovskyy A. S., Caoili S. E. C., Ionov Y., Piontkivska H., Skums P., Tsyvina V., Zelikovskij A. Z., Waghela S. D.
Infection and Immunity
Vol.87, Issue8, Num.e00246
Опубликовано: 2019
Тип ресурса: Статья

DOI:10.1128/IAI.00246-19

Аннотация:
Lyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused by Borreliella burgdorferi. No vaccine is available for humans. Dogmatically, B. burgdorferi can establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies. However, our recent study has shown that the B. burgdorferi spirochete is effectively cleared by anti-B. burgdorferi antibodies of New Zealand White rabbits, despite the surface expression of VlsE. Besides homologous protection, the rabbit antibodies also crossprotect against heterologous B. burgdorferi spirochetes and significantly reduce the pathology of LD arthritis in persistently infected mice. Thus, this finding that NZW rabbits develop a unique repertoire of very potent antibodies targeting the protective surface epitopes, despite abundant VlsE, prompted us to identify the specifici
Ключевые слова:
Borrelia burgdorferi; Lyme disease; Next-generation sequencing; Phage display; Protection; Subtractive reverse vaccinology; Surface epitopes; VlsE
epitope; membrane protein; outer membrane protein; rabbit antiserum; bacterial antigen; bacterial protein; bacterial vaccine; bacterium antibody; epitope; lipoprotein; outer membrane protein; subunit vaccine; VlsE protein, Borrelia burgdorferi; amino acid sequence; animal experiment; animal model; antibody response; Article; bacterial strain; Borrelia afzelii; Borrelia burgdorferi; Borrelia garinii; carboxy terminal sequence; comparative study; consensus sequence; controlled study; cross reaction; in vitro study; Lyme disease; male; mouse; New Zealand White (rabbit); next generation sequencing; nonhuman; nuclear magnetic resonance; phage display; priority journal; Saccharomyces cerevisiae; skin biopsy; surface property; animal; C3H mouse; immunology; Leporidae; Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Vaccines; Borrelia burgdorferi; Epitopes; Lipoproteins; Male; Mice; Mice, Inbred C3H; Rabbits; Vaccines, Subun
Язык текста: Английский
ISSN: 1098-5522
Rogovskyy A. S.
Caoili S. E. C.
Ionov Y.
Piontkivska H.
Skums P.
Tsyvina V.
Zelikovskij A. Z. Aleksandr Zinovij 1960-
Waghela S. D.
Роговскyy А. С.
Cаоили С. Е. C.
Ионов Y.
Пионткивска Х.
Скумс П.
Цyвина В.
Зеликовский А. З. Александр Зиновий 1960-
Wагхела С. Д.
Delineating surface epitopes of lyme disease pathogen targeted by highly protective antibodies of New Zealand white rabbits
Текст визуальный непосредственный
Infection and Immunity
American Society for Microbiology
Vol.87, Issue8 Num.e00246
2019
Статья
Borrelia burgdorferi Lyme disease Next-generation sequencing Phage display Protection Subtractive reverse vaccinology Surface epitopes VlsE
epitope membrane protein outer membrane protein rabbit antiserum bacterial antigen bacterial protein bacterial vaccine bacterium antibody epitope lipoprotein outer membrane protein subunit vaccine VlsE protein, Borrelia burgdorferi amino acid sequence animal experiment animal model antibody response Article bacterial strain Borrelia afzelii Borrelia burgdorferi Borrelia garinii carboxy terminal sequence comparative study consensus sequence controlled study cross reaction in vitro study Lyme disease male mouse New Zealand White (rabbit) next generation sequencing nonhuman nuclear magnetic resonance phage display priority journal Saccharomyces cerevisiae skin biopsy surface property animal C3H mouse immunology Leporidae Animals Antibodies, Bacterial Antigens, Bacterial Bacterial Outer Membrane Proteins Bacterial Proteins Bacterial Vaccines Borrelia burgdorferi Epitopes Lipoproteins Male Mice Mice, Inbred C3H Rabbits Vaccines, Subun
Lyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused by Borreliella burgdorferi. No vaccine is available for humans. Dogmatically, B. burgdorferi can establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies. However, our recent study has shown that the B. burgdorferi spirochete is effectively cleared by anti-B. burgdorferi antibodies of New Zealand White rabbits, despite the surface expression of VlsE. Besides homologous protection, the rabbit antibodies also crossprotect against heterologous B. burgdorferi spirochetes and significantly reduce the pathology of LD arthritis in persistently infected mice. Thus, this finding that NZW rabbits develop a unique repertoire of very potent antibodies targeting the protective surface epitopes, despite abundant VlsE, prompted us to identify the specifici