Protective efficacy against respiratory syncytial virus following murine neonatal immunization with BBG2Na vaccine: influence of adjuvants and maternal antibodies.
Alum-adsorbed BBG2Na, a recombinant vaccine derived in part from the respiratory syncytial virus (RSV) subgroup A G protein, induced moderate antibody titers after 1 immunization in 1-week-old mice but conferred complete lung protection upon RSV challenge. The anti-BBG2Na IgG1-IgG2a neonatal isotype profile was suggestive of dominant Th2 responses compared with those in adults. Formulation of BBG2Na with a Th1-driving adjuvant efficiently shifted neonatal responses toward a more balanced and adultlike IgG1-IgG2a profile without compromising its protective efficacy. BBG2Na-induced protective immunity was maintained even after early life immunization in the presence of high titers of maternal antibodies. Under these conditions, the protective efficacy (86%-100%) reflected the high capacity of the nonglycosylated G2Na immunogen to escape inhibition by RSV-A-induced maternal antibodies. Thus, immunization with BBG2Na protected against viral challenge despite neonatal immunologic immaturity and the presence of maternal antibodies, two major obstacles to neonatal RSV vaccine development.
Siegrist
C A
CA
World Health Organization Collaborating Center for Neonatal Vaccinology, University of Geneva, 1211 Geneva 4, Switzerland. siegrist@cmu.unige.ch
Plotnicky-Gilquin
H
H
Córdova
M
M
Berney
M
M
Bonnefoy
J Y
JY
Nguyen
T N
TN
Lambert
P H
PH
Power
U F
UF
D000276:Adjuvants, Immunologic; D000818:Animals; D000831:Animals, Newborn; D015707:HN Protein; D007112:Immunity, Maternally-Acquired; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000627:therapeutic use; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000627:therapeutic use*; D014765:Viral Vaccines / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D015707:HN Protein; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G