Cross-protective pathogen protection, methods and compositions thereof
The present disclosure provides a method of inducing a cross-protective immune response in a subject against a pathogen, such as influenza, comprising administering a first unique pathogen antigen to the subject; and administering a second unique pathogen antigen 3-52 weeks after a); wherein the second unique pathogen antigen and the first unique pathogen antigen are immunologically distinct but share conserved sites that are not normally immunogenic for antibodies. Also disclosed herein are assays for detecting cross-protective antibodies, methods of generating novel cross-protective antibodies. Further provided are novel antibodies against influenza.
1. An antibody or antibody fragment comprising the light chain CDR sequences of SEQ ID NOS:17, 18 and 19 or variants thereof and/or the heavy chain CDR sequences of SEQ ID NOS:20, 21 and 22 or variants thereof, or comprising the light chain variable region as shown in the amino acid sequence of SEQ ID NO: 23 or a variant thereof and/or the heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:24 or a variant thereof.
2. A method of treating or preventing an influenza viral infection comprising administering the antibody or antibody fragment of claim 1 to a subject.
3. A method of generating monoclonal antibodies cross-protective against influenza comprising:
(a) isolating cells from a sample of blood or other tissue containing cells of the immune system from a subject that has been infected or vaccinated with an influenza strain that exhibits a unique hemagglutinin;
(b) preparing monoclonal antibodies using the cells of (a); and
(c) selecting monoclonal antibodies that cross-react with different strains and subtypes of viruses or that bind to the stem of the hemagglutinin.
4. The method of claim 3 , wherein the method further comprises selecting for antibody secreting cells that produce the desired antibody prior to b).