Fully human monoclonal antibodies from antibody secreting cells after vaccination with Pneumovax®23 are serotype specific and facilitate opsonophagocytosis.
B lymphocyte memory generates antibody-secreting cells (ASCs) that represent a source of protective antibodies that may be exploited for therapeutics. Here we vaccinated four donors with Pneumovax®23 and produced human monoclonal antibodies (hmAbs) from ASCs. We have cloned 137 hmAbs and the specificities of these antibodies encompass 19 of the 23 serotypes in the vaccine, as well as cell wall polysaccharide (CWPS). Although the majority of the antibodies are serotype specific, 12% cross-react with two serotypes. The Pneumovax®23 ASC antibody sequences are highly mutated and clonal, indicating an anamnestic response, even though this was a primary vaccination. Hmabs from 64% of the clonal families facilitate opsonophagocytosis. Although 9% of the total antibodies bind to CWPS impurity in the vaccine, none of these clonal families showed opsonophagocytic activity. Overall, these studies have allowed us to address unanswered questions in the field of human immune responses to polysaccharide vaccines, including the cross-reactivity of individual antibodies between serotypes and the percentage of antibodies that are protective after vaccination with Pneumovax®23.
Oklahoma Medical Research Foundation, Arthritis and Clinical Immunology Research Program, Oklahoma City, OK 73104, USA. smithk@omrf.org
Kenneth
K
Smith
Jennifer J
JJ
Muther
Angie L
AL
Duke
Emily
E
McKee
Nai-Ying
NY
Zheng
Patrick C
PC
Wilson
Judith A
JA
James
D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology*; D002999:Clone Cells; D003429:Cross Reactions; D005260:Female; D018922:HL-60 Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D009895:Opsonin Proteins / Q000737:chemistry / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000276:immunology; D014611:Vaccination
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial