Safety and efficacy of immune-stimulating complex-based antigen delivery systems for neonatal immunisation against respiratory syncytial virus infection.
To protect against human respiratory syncytial virus (hRSV)-induced bronchiolitis in early infancy, vaccines need to be designed which are effective in the neonatal period. To test the safety and efficacy of adjuvants in neonatal mice, we injected hRSV surface proteins combined with immune-stimulating complexes (ISCOMs) prepared from fractions A, C or A + C of Quillaja saponins. All were well tolerated in adults, but A + C ISCOMS proved lethal in neonates; A or C fractions alone were well tolerated by neonates up to the adult dose. hRSV-ISCOM A induced antibody responses similar to combined fractions, and potent in vitro cytotoxic T cell responses. Adult-like in vitro cytotoxicity against hRSV-infected targets and precursor cytotoxic T cell frequencies were observed within one week of neonatal priming and hRSV-ISCOM A-primed neonates showed virtually complete protection against subsequent viral challenge. hRSV challenge was associated with some pulmonary eosinophilia in both age groups, with higher IL-4 production by lung CD4+ T cells in mice primed as neonates. This was, however, accompanied by only minor (approximately 10%) and transient illness and weight loss. Thus, the identification of hRSV antigen delivery systems with an age-appropriate adjuvanticity/reactogenicity balance may be feasible even in the vulnerable early-life period.
Regner
Matthias
M
WHO Collaborating Center for Vaccinology, Department of Pathology, University of Geneva, CMU, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland.
Culley
Fiona
F
Fontannaz
Paola
P
Hu
Kefei
K
Morein
Bror
B
Lambert
Paul-Henri
PH
Openshaw
Peter
P
Siegrist
Claire-Anne
CA
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000097:blood; D001990:Bronchiolitis, Viral / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D016882:ISCOMs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016882:ISCOMs; D022261:Respiratory Syncytial Virus Vaccines; D012503:Saponins