Following the 2016 ECF Consortium annual meeting in May 2016, participants in the project drafted short blog posts about different aspects of their work related to East Coast fever (ECF) vaccine development. This post was contributed by William C. Davis, Lindsay M. Fry, and Donald P. Knowles (Washington State University).
The WSU monoclonal antibody (mAb) center was established in 1982 with a focus on developing mAb reagents for use in research. It became a formal service center of the Washington State University and CVM in 2012.
It now operates as a non-profit service center with primary support derived from services and direct sale of mAbs through the center and sale of mAbs as OEMs (original equipment manufacturer) to for-profit companies for resale at a modest discount. This arrangement provides an opportunity for for-profit companies to contribute to research and development without excessive investment of resources.
The repository currently contains hybridomas developed by the center, ILRAD/ILRI, the Basel Institute of Immunology (that dissolved years ago), USDA/NIH, and hybridomas donated by individual investigators. The hybridomas include mAbs specific for known leukocyte differentiation molecules and hybridomas left over from the international workshops, convened to collaborate in development and characterization of mAbs for use in large animal research, that await full characterization of their specificity.
The mAbs currently available for research in cattle are listed in Table I.
Many gaps remain in reagents needed to conduct research on vaccines and the immune-pathogenesis of pathogens and parasites, especially for Theileria parva and mycobacterial pathogens M. bovis and M. paratuberculosis. These include transcription factors regulating T and B cell differentiation, cytokine and chemokine receptors that are associated with trafficking and differentiation of T cells with different effector and regulatory activity. This also includes receptors involved in uptake and processing of antigens expressed on antigen presenting cells (dendritic cells and macrophages). Current efforts are focused on development of reagents critically needed for investigation of the immune response to Theileria parva.
Table II lists the reagents currently under development or planned.
Table I. Monoclonal antibodies for use in cattle
Catalog # | Clone | Description | Ig isotype |
BOV2001 | H58A | MHC CL I | G2a |
BOV2002 | PT85A | MHC CL I | G2a |
BOV2122 | B5C | MHC CL I | G2b |
BOV2125 | W6/32 | MHC CL I | G2a |
BOV2120 | H1A | MHC CL I | G2a |
BOV2131 | H6A | MHC CL I | G2a |
BOV2003 | H42A | MHC CL II | G2a |
BOV2004 | TH14B | MHC CL II BoLA-DR | G2a |
BOV2005 | TH81A | MHC CL II BoLA-DQ | G2a |
BOV2117 | H34A | MHC CL II | G2b |
BOV2114 | BAQ150A | MHC CL II | G3 |
BOV2115 | TH16A | MHC CL II | G2a |
BOV-CT2012 | CAT82A | MHC CL II | G1 |
BOV2007 | BAQ95A | CD2 | G1 |
BOV2008 | MUC2A | CD2 | G2a |
BOV2113 | 16-1E10 | CD2 | G1 |
BOV2123 | CH134A | CD2 | G1 |
BOV2009 | MM1A | CD3 | G1 |
BOV2010 | IL11A | CD4 | G2a |
BOV2011 | GC50A | CD4 | M |
BOV2012 | CACT138A | CD4 | G1 |
BOV2116 | CACT83B | CD4 | M |
BOV2013 | B29A | CD5 | G2a |
BOV2014 | CACT105A | CD5 | G1 |
BOV2015 | BAQ91A | CD6 | G1 |
BOV2016 | BAQ83A | CD6 | G2b |
BOV2017 | CACT80C | CD8α | G1 |
BOV2018 | CACT130A | CD8α | G3 |
BOV2019 | 7C2B | CD8α | G2a |
BOV2097 | BAQ111A | CD8α | M |
BOV2020 | BAT82A | CD8β | G1 |
BOV2021 | RH1A | CD9 | G3 |
BOV2111 | B18A | CD9 | G3 |
BOV2112 | LT86A | CD9 | G2a |
BOV2023 | HUH73A | CD11a | G1 |
BOV2024 | MM10A | CD11b | G2b |
BOV2025 | MM12A | CD11b | G1 |
BOV2026 | BAQ153A | CD11c | M |
BOV2066 | BAQ151A | CD11c | G1 |
BOV2124 | MM31A | CD11c | M |
BOV2027 | CAM36A | CD14 | G1 |
BOV2028 | CAM66A | CD14 | M |
BOV2109 | MM61A | CD14 | G1 |
BOV2029 | BAQ30A | CD18 | G1 |
BOV2030 | HUH82A | CD18 | G2a |
BOV2031 | GB25A | CD21 | G1 |
BOV2032 | BAQ15A | CD21 | M |
BOV2073 | CACT108A | CD25 | G2a |
BOV2074 | CACT116A | CD25 | G1 |
BOV2075 | GB112A | CD25 | G1 |
BOV2076 | LCTB2A | CD25 | G3 |
BOV2077 | LCTB32A | CD25 | M |
BOV2078 | CACT114A | CD26 | G2b |
BOV2136 | NK29A | CD26 | G1 |
BOV2137 | NK47A | CD26 | G2a |
BOV2033 | TE1A | CD28 | M |
BOV2034 | FW4-101 | CD29 | G1 |
BOV2107 | ILA158A | CD40 | G1 |
BOV2036 | CAPP2A | CD41 | G1 |
BOV2037 | BAG40A | CD44 | G3 |
BOV2038 | BAT31A | CD44 | G1 |
BOV2039 | CACTB51A | CD45 | G2a |
BOV2040 | GS5A | CD45R | G1 |
BOV2041 | GC6A | CD45R | M |
BOV2042 | ILA116A | CD45R0 | G3 |
BOV2043 | GC42A | CD45R0 | G1 |
BOV2044 | HUH71A | CD47 | G1 |
BOV2045 | TH17A | CD47 | M |
BOV2079 | FW3-218 | CD49d | G2b |
BOV2134 | CACT180A | CD50 | G1 |
BOV2135 | CACT216A | CD50 | M |
BOV2046 | BAQ92A | CD62L | G1 |
BOV2080 | KTSN7A | CD69 | G1 |
BOV2081 | ILA77A | CD71 | M |
BOV2127 | ILA159 | CD80 | G1 |
BOV2128 | ILA190A | CD86 | G1 |
BOV2141 | LND68A | CD163 | G1 |
BOV2065 | LND37A | CD163 | G1 |
BOV2049 | DH59B | CD172a | G1 |
BOV2105 | ILA53A | CD205 | G2a |
BOV2106 | ILA114A | CD205 | G1 |
BOV2133 | 209MD26A | CD209 | G2a |
BOV2058 | GB21A | TCR1-N24 d chain specific | G2b |
BOV2059 | CACT61A | TCR1-N12 d chain specific | M |
BOV2056 | CACTB6A | TCR1-N6 γ chain specific? | M |
BOV2057 | CACTB81A | TCR1-N7 γ chain specific? | G1 |
BOV2050 | B7A | WC1+ γδ T cell N1 epitope | M |
BOV2053 | BAQ4A | WC1+ γδ T cell N2 epitope | G1 |
BOV2052 | GB54A | WC1+ γδ T cell N25 epitope | G2a |
BOV2054 | CACTB32A | WC1+ γδ T cell N3epitope | G1 |
BOV2121 | CACTB7A | WC1+ γδ T cell N3 subset | G1 |
BOV2055 | BAQ89A | WC1+ γδ T cell N4 epitope | G1 |
BOV2119 | BAQ159A | WC1+ γδ T cell N4 subset | G1 |
BOV2093 | BAG2B | WC1+ γδ T cell N27 epitope | M |
BOV2094 | BAG25A | WC1+ γδ T cell N28 epitope | M |
BOV2098 | CACTB21A | WC1+ γδ T cell N29 epitope | G1 |
BOV2099 | CACTB31A | WC1+ γδ T cell N30 epitope | G2b |
BOV2101 | CACT21A | WC1+ γδ T cell N31 epitope | G1 |
BOV2118 | ILA29 | WC1+ γδ T cell | G1 |
BOV2060 | PIG45A | sIgM | G2b |
BOV2061 | BIG73A | sIgM | G1 |
BOV2062 | BIG715A | IgG1 | G1 |
BOV2145 | BIG312D3 | IgA | G1 |
BOV2063 | BIG501E | l light chain | G1 |
BOV2064 | BAQ44A | B cells | M |
BOV2102 | GB26A | B cells | M |
BOV2126A | BAQ155A | B cells (sIgM?) | G1 |
BOV2067 | CH138A | Neutrophils | M |
BOV2068 | MM20A | Neutrophils = CH138A | G1 |
BOV2070 | BIB | ab and gd T cells | M |
BOV2071 | TH18A | Pan lymphocyte | G3 |
BOV2072 | GB50A | Pan leukocyte, endothelial cells | G1 |
BOV2082 | CACT200A | SLAMF9 (ACT 1) | G1 |
BOV2083 | CACT206A | SLAMF9 (ACT 1) | G2a |
BOV2092 | FOX5A | Foxp3 | G1 |
BOV2103 | GB53A | Gr, mono/ lymph sub | G1 |
BOV2104 | GC34A | Lymphocytes, monocytes | M |
BOV2132 | NK64A | Gp96 | G1 |
BOV2138 | BAQ56A | Platelets | G1 |
BOV2139 | BAQ125A | Platelets | G2b |
BOV2140 | GC5A | Platelets | G1 |
Table II. Current status of mAb development program
Molecule | Specificity | Status |
APC | ||
CD209 | Immature DC | Validated |
CD83 | Mature DC | In process |
CD135 | Flt-3 | Planned |
CD282 | TLR2 | Cross reactive mAb available |
CD284 | TLR4 | Planned |
Phenotype markers | ||
CD | IL-12R | Validating specificity |
CD | IL-23R | Validating specificity |
CD161 | Natural Killer Cell Surface Protein P1A | Validating specificity |
CD358 | IL-21R | In process, hybridomas just produced |
CD126 | IL-6R | Planned |
CD210a | IL-10RA | Planned |
Activation markers | ||
CD69 | Early activation | Validated |
CD154 | CD40L | Validating specificity |
CD152 | CTL-4 | In process, ready for fusion |
Regulatory | ||
FoxP3 (transcription factor) | Treg | Validated |
GARP (surface protein) | Glycoprotein A Repetitions Predominant | Validating specificity |
Functional status | ||
CD95 | Death receptor | |
CD178 | DR FASL | |
CD273 | PD-L2 | |
CD274 | PD-L1 | |
CD279 | PD1 | |
CD223 | LAG-3 | |
CD366 | TIM-1 | |
Traficking | ||
CD192 | CCR2 | Planned |
CD195 | CCR5 | Planned |
CD196 | CCR6 | Validating specificity |
CD197 | CCR7 | Cross reactive mAb available |
CD354 | TREM-1 | Myeloid cells |
Cytokines | ||
IFN-γ | Validated | |
IL-17 | Validated | |
IL-1β | Validated | |
GM-CSF | Validated |