Human metapneumovirus combination vaccine
AssigneeValneva SE
InventorsUrban Lundberg, Andreas Meinke, Fabien Perugi
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Abstract
The present invention relates to a vaccine composition for preventing and/or treating a respiratory system infection such as a human metapneumovirus infection of the respiratory system. This vaccine composition comprises two or more modified human metapneumovirus (hMPV) F proteins or variants thereof provided in a pre-fusion and/or post-fusion conformation form.
Claims77
An immunogenic composition comprising a combination of a stabilized pre-fusion and post-fusion conformation forms of the human metapneumovirus (hMPV) F protein or fragments thereof, wherein said pre- and post-fusion F proteins or fragments thereof are derived from the same or different genotypes A and B.
The immunogenic composition of any of preceding claim, wherein the pre-fusion and post-fusion F proteins are recombinant proteins.
The immunogenic composition of any preceding claim, wherein the F protein lacks the cytoplasmic tail and/or transmembrane domain.
The immunogenic composition of any preceding claim, wherein the pre- and/or post-fusion F protein has an amino acid sequence, which is a modified amino acid sequence of the native F protein derived from any hMPV strain or clinical isolate.
The immunogenic composition of any preceding claim, wherein the pre- and/or post-fusion F protein comprises at least one mutation (substitution or deletion), preferably up to 10 mutations, relative to the native F protein sequence of SEQ ID NO:
- 1 to 10 and 49.
The immunogenic composition of any preceding claim, wherein the pre-fusion F protein comprises one or more amino acid substitution(s) to cysteine, which introduce one or more non-native disulfide bond(s) that stabilize the pre-fusion conformation.
The immunogenic composition of any preceding claim, wherein the pre-fusion F protein consists of a single polypeptide chain stabilized by at least one non-natural disulfide bond.
The immunogenic composition of any preceding claim, wherein the pre- and post-fusion hMPV F protein comprises a trimerization helper domain (foldon) having the sequence of SEQ ID NO:
- 23 to 28 or a variant thereof.
The immunogenic composition of any preceding claim, wherein the F protein is produced as a homo- or hetero-trimer.
The immunogenic composition of any preceding claim, wherein the composition comprises a further hMPV antigen.
The immunogenic composition of any preceding claim, wherein the composition further comprises at least one pharmaceutically acceptable carrier and/or excipient.
The immunogenic composition of any preceding claim, wherein the composition further comprises an adjuvant.
The immunogenic composition of any preceding claim, wherein the composition is capable to elicit neutralizing antibodies against the pre-fusion and/or post-fusion F protein(s).
The immunogenic composition of any preceding claim, wherein the composition provides a superior immune response (neutralizing antibody titers) as compared to immune response (neutralizing antibody titers) elicited by a composition comprising either the pre- or post-fusion F protein used at the same total protein amount.
The immunogenic composition of any preceding claim, wherein the composition provides protection against infection with at least one, preferably more than one homologous or heterologous hMPV strain.
The immunogenic composition of any preceding claim, wherein the composition is a vaccine.
The immunogenic composition according to any preceding claim for use as a medicament.
The immunogenic composition according to any preceding claim for treating and/or preventing hMPV infection and associated disease in a subject.
Dependencies are inferred from the claim text.