Antibodies that neutralize rsv, mpv and pvm and uses thereof

Abstract

The invention relates to antibodies, and antigen binding fragments thereof, that neutralize infection of both RSV, MPV and PVM. The invention also relates to nucleic acids that encode, immortalized B cells and cultured plasma cells that produce, and to polypeptides that bind to such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies, antibody fragments, and polypeptides recognized by the antibodies of the invention in screening methods as well as in the diagnosis, treatment and prevention of RSV or MPV infection and RSV and MPV co-infection.

1 .- 32 . (canceled) 
     
     
         33 . A method of treating an RSV infection, a MPV infection, or both, in a subject, the method comprising administering to the subject an effective amount of an antibody, or an antigen-binding fragment thereof, that specifically binds a polypeptide having the amino acid sequence of any one of SEQ ID NOs:64-69. 
     
     
         34 . The method of  claim 33 , wherein the RSV comprises group A RSV, group B RSV, or both, and wherein the MPV comprises group A MPV, group B MPV, or both. 
     
     
         35 . The method of  claim 33 , wherein the subject is human. 
     
     
         36 . The method of  claim 33 , wherein the RSV comprises bRSV. 
     
     
         37 . The method of  claim 36 , wherein the subject is a cow. 
     
     
         38 . The method of  claim 33 , wherein the effective amount comprises from about 0.01 mg/kg to about 50 mg/kg. 
     
     
         39 . The method of  claim 38 , wherein the effective amount comprises from about 0.05 mg/kg to about 10 mg/kg. 
     
     
         40 . The method of  claim 33 , wherein the antibody, or an antigen-binding fragment thereof, specifically binds to an F protein of PVM. 
     
     
         41 . A method of detecting an RSV infection, a MPV infection, or both, in a subject, the method comprising:
 (i) contacting a sample from the subject with an antibody, or an antigen-binding fragment thereof, that specifically binds a polypeptide having the amino acid sequence of any one of SEQ ID NOs:64-69; and   (ii) detecting an antigen/antibody complex,   thereby detecting the presence of an RSV infection, a MPV infection, or both.   
     
     
         42 . The method of  claim 41 , wherein the sample comprises a sample from one or more of a nasal passage, a sinus cavity, a salivary gland, a lung, a liver, a pancreas, a kidney, an ear, an eye, a placenta, an alimentary tract, a heart, an ovary, a pituitary gland, an adrenal gland, a thyroid gland, a brain, or skin. 
     
     
         43 . A method of generating an immune response in a subject, the method comprising administering to the subject:
 (i) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:63;   (ii) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:64;   (iii) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:65;   (iv) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:66;   (v) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:67;   (vi) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:68;   (vii) a polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:69; or   (viii) any combination of (i)-(vii).   
     
     
         44 . The method of  claim 43 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:63. 
     
     
         45 . The method of  claim 43 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:64. 
     
     
         46 . The method of  claim 43 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:65. 
     
     
         47 . The method of  claim 43 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:66. 
     
     
         48 . The method of  claim 43 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:67. 
     
     
         49 . The method of  claim 43 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:68. 
     
     
         50 . The method of  claim 43 , wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO:69. 
     
     
         51 . The method of  claim 43 , wherein the subject is a mammal. 
     
     
         52 . The method of  claim 51 , wherein the subject is a human. 
     
     
         53 . The method of  claim 43 , wherein the immune response comprises an antibody specific for the administered immunogenic polypeptide. 
     
     
         54 . The method of  claim 53 , further comprising isolating the antibody from the subject. 
     
     
         55 . A method for screening serum of a subject for an antibody, the method comprising:
 (i) contacting serum from the subject with a composition comprising a polypeptide that consists of the amino acid sequence set forth in any one of SEQ ID NOs:63-69; and   (ii) screening the serum for an antibody that is immunoreactive with the polypeptide.   
     
     
         56 . A method for monitoring the quality of an anti-RSV vaccine or an anti-MPV vaccine, the method comprising:
 (i) contacting the vaccine with an antibody or antigen-binding fragment thereof that specifically binds a polypeptide having the amino acid sequence of any one of SEQ ID NOs:64-69;   (ii) determining whether the antibody or antigen-binding fragment forms an antigen/antibody complex with the vaccine.   
     
     
         57 . A method of treating an RSV infection, a MPV infection, or both, in a subject, the method comprising administering to the subject an effective amount of an antibody, or an antigen-binding fragment thereof, that specifically binds a conserved region in the amino terminal portion of an F protein of RSV, MPV, and PVM. 
     
     
         58 . The method of  claim 57 , wherein the conserved region on the amino terminal portion of the F protein of RSV, MPV, and PVM consists of an amino acid sequence of formula Y(X 1 )S(X 2 )LRTGW (SEQ ID NO:70), wherein (X 1 ) is an amino acid selected from L, F, or K, and (X 2 ) is an amino acid selected from A or V.