Stabilized soluble pre-fusion rsv f polypeptides

A recombinant pre-fusion respiratory syncytial virus (RSV) Fusion (F) polypeptide comprising:

• at least one epitope that is specific to the pre-fusion conformation F protein, wherein the at least one epitope is recognized by
• a pre-fusion specific monoclonal antibody, antibody comprising:
• a heavy chain CDR1 region of SEQ ID NO:
• 54,
• a heavy chain CDR2 region of SEQ ID NO:
• 55,
• a heavy chain CDR3 region of SEQ ID NO:
• 56,
• a light chain CDR1 region of SEQ ID NO:
• 62,
• a light chain CDR2 region of SEQ ID NO:
• 63, and
• a light chain CDR3 region of SEQ ID NO:
• 64, and/or
• a pre-fusion specific monoclonal antibody, antibody comprising:
• a heavy chain CDR1 region of SEQ ID NO:
• 58,
• a heavy chain CDR2 region of SEQ ID NO:
• 59,
• a heavy chain CDR3 region of SEQ ID NO:
• 60,
• a light chain CDR1 region of SEQ ID NO:
• 66,
• a light chain CDR2 region of SEQ ID NO:
• 67, and
• a light chain CDR3 region of SEQ ID NO:
• 68;
• and
• an F1 domain and an F2 domain, said F1 and F2 domains comprising at least one mutation, as compared to wild-type F1 and F2 domains, selected from the group consisting of:
• (a) a mutation of the amino acid residue at position 161;
• (b) a mutation of the amino acid residue at position 182;
• (c) a mutation of the amino acid residue at position 173;
• and
• (d) a mutation of the amino acid residue D at position 486 into C (D486C) in combination with a mutation of the amino acid residue D at position 489 into C (D489C) or a mutation of the amino acid residue E at position 487 into C (E487C).