A novel bipolar mode of attachment to aluminium-containing adjuvants by BBG2Na, a recombinant subunit hRSV vaccine.
Human respiratory syncytial virus (hRSV) is a major pathogen responsible for bronchiolitis and severe pulmonary disease in very young children, immunodeficient patients and the elderly. BBG2Na, a recombinant chimeric protein produced in Escherichia coli, is a promising subunit vaccine candidate against this respiratory pathogen, composed of G2Na, the central domain of RSV G glycoprotein, and BB, an albumin binding domain of streptococcal protein G. BBG2Na has a basic isoelectric point (pI 9.3) and as expected, is strongly adsorbed by aluminium phosphate (AP). Surprisingly, BBG2Na is also strongly adsorbed by aluminium hydroxide (AH), which normally binds molecules with acidic isoelectric points. This behaviour was unexpected according to the well established adsorption model of Hem and co-workers. Our observations may be explained by the bipolar two-domain structure of the BBG2Na chimera which is not reflected by the global basic isoelectric point of the whole protein: the BB domain has an acidic isoelectric point (pI 5.5) and the G2Na domain a highly basic one (pI 10.0). Importantly, formulation in either aluminium salt resulted in equally high immunogenicity and protective efficacy against RSV in mice. From a physicochemical point of view, this unique property of BBG2Na makes it eminently suitable for combination to either paediatric or elderly multivalent AH- or AP-containing vaccines already in the market or in development.
Dagouassat
N
N
BioMérieux-Pierre Fabre, Centre d'Immunologie Pierre-Fabre, 5 Av. Napoléon III, BP 497, F74164, Saint-Julien-en-Genevois, France.
Robillard
V
V
Haeuw
J F
JF
Plotnicky-Gilquin
H
H
Power
U F
UF
Corvaïa
N
N
Nguyen
T
T
Bonnefoy
J Y
JY
Beck
A
A
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000327:Adsorption; D017607:Aluminum Compounds / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D002021:Buffers; D019855:Ethylene Glycol / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010710:Phosphates / Q000008:administration & dosage*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D002021:Buffers; D010710:Phosphates; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D000536:Aluminum Hydroxide; C012714:aluminum phosphate; D019855:Ethylene Glycol