The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease.
Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture.
Pfizer Biotherapeutics Pharmaceutical Sciences, 1 Burtt Rd., Andover, Massachusetts, USA. yin.luo@pfizer.com.
Yin
Y
Luo
Pfizer Biotherapeutics Pharmaceutical Sciences, 700 Chesterfield Pkwy W, St. Louis, Missouri, USA.
Olga V
OV
Friese
Pfizer Biotherapeutics Pharmaceutical Sciences, 700 Chesterfield Pkwy W, St. Louis, Missouri, USA.
Herbert A
HA
Runnels
Pfizer Vaccine Research and Development, 401 N. Middletown Rd., Pearl River, New York, USA.
Lakshmi
L
Khandke
Pfizer Vaccine Research and Development, 401 N. Middletown Rd., Pearl River, New York, USA.
Gary
G
Zlotnick
Pfizer Worldwide Research, 558 Eastern Point Rd., Groton, Connecticut, USA.
Ann
A
Aulabaugh
Pfizer Biotherapeutics Pharmaceutical Sciences, 401 N. Middletown Rd., Pearl River, New York, USA.
Thomas
T
Gore
Pfizer Vaccine Research and Development, 401 N. Middletown Rd., Pearl River, New York, USA.
Eugene
E
Vidunas
Pfizer Biotherapeutics Pharmaceutical Sciences, 1 Burtt Rd., Andover, Massachusetts, USA.
Stephen W
SW
Raso
Pfizer Vaccine Research and Development, 401 N. Middletown Rd., Pearl River, New York, USA.
Elena
E
Novikova
Pfizer Biotherapeutics Pharmaceutical Sciences, 700 Chesterfield Pkwy W, St. Louis, Missouri, USA.
Emilia
E
Byrne
Pfizer Biotherapeutics Pharmaceutical Sciences, 700 Chesterfield Pkwy W, St. Louis, Missouri, USA.
Michael
M
Schlittler
Pfizer Biotherapeutics Pharmaceutical Sciences, 700 Chesterfield Pkwy W, St. Louis, Missouri, USA.
Donald
D
Stano
Pfizer Biotherapeutics Pharmaceutical Sciences, 1 Burtt Rd., Andover, Massachusetts, USA.
Robert L
RL
Dufield
Pfizer Biotherapeutics Pharmaceutical Sciences, 700 Chesterfield Pkwy W, St. Louis, Missouri, USA.
Sandeep
S
Kumar
Pfizer Vaccine Research and Development, 401 N. Middletown Rd., Pearl River, New York, USA.
Annaliesa S
AS
Anderson
Pfizer Vaccine Research and Development, 401 N. Middletown Rd., Pearl River, New York, USA.
Kathrin U
KU
Jansen
Pfizer Biotherapeutics Pharmaceutical Sciences, 1 Burtt Rd., Andover, Massachusetts, USA. jason.rouse@pfizer.com.
Jason C
JC
Rouse
D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000502:physiology*; D008074:Lipoproteins / Q000502:physiology*; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D015394:Molecular Structure; D011499:Protein Processing, Post-Translational
D008055:Lipids; D008074:Lipoproteins; D022401:Meningococcal Vaccines
Neisseria meningitidis serogroup B; bivalent rLP2086; factor H binding protein; meningococcal meningitis B vaccine; self-adjuvanting vaccine