# US 2019/0167783 A1 · Vaccine > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167783 A1 - Document ID: US20190167783A1 - Status: Published application - Kind: A1 - Application number: 16/155,018 - Filed: 2018-10-09 - Published: 2019-06-06 - Earliest claimed: 2011-10-03 - Assignees: Duke University; Children's Medical Center Corporation - Applicants: Duke University; Children's Medical Center Corporation - Inventors: Barton F. HAYNES; Garnett KELSOE; Stephen HARRISON; Thomas B. KEPLER - Web page: https://patentgrep.com/patent/US20190167783A1 ## CPC - A61K 39/21: Retroviridae, e.g. equine infectious anemia virus - A61K 39/12: Viral antigens - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/18: for HIV - C07K 16/1145: {Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site} - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - G16B 5/00: ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks - G16B 5/20: Probabilistic models - A61K 2039/55511: {Organic adjuvants} - A61K 2039/70: {Multivalent vaccine} - C12N 2740/16034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2740/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2770/00034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The present invention relates, in general, to an HIV-1 vaccine and, in particular, to a B cell lineage-based vaccination protocol. ## Claims ### Claim at position 1 -6. (canceled) ### Claim 7 A method to identify prime and boost immunogens for use in a B cell lineage-based vaccination protocol comprising: i) identifying pairs of variable heavy (VH) and variable light (VL) chain sequences expressed as B-cell receptors by a single cell of clonally related B cells from a subject producing broad neutralizing antibodies (bnAbs), including a pair of VH and VL chain sequences of a mature bnAb, ii) inferring from the sequences of step (i), a pair of VH and VL chains of an unmutated ancestor antibody (UA) of the mature bnAb, and one or more pairs of VH and VL chains of likely intermediate antibodies (IAs) of the mature bnAb, iii) expressing the pair of VH and VL chains of the UA inferred in step (ii) to produce the UA, and expressing the one or more pairs of VH and VL chains of the one or more likely IAs inferred in step (ii) to produce the one or more likely IAs, iv) performing one or more UA binding assays, wherein the binding affinity of the expressed UA of step (iii) for one or more immunogens is determined, v) identifying a first immunogen with a binding affinity for the UA determined in step (iv), wherein the first immunogen is identified as a prime immunogen, vi) performing one or more IA binding assays, wherein the binding affinity of the one or more expressed likely IAs of step (iii) for one or more immunogens is determined, wherein the one or more immunogens comprises the first immunogen identified as the prime immunogen in step (v), and vii) identifying one or more second immunogens with enhanced binding affinity for the one or more likely IAs relative to the first immunogen of step (v), wherein the one or more second immunogens is identified as one or more boost immunogens, wherein the first immunogen identified as a prime immunogen has an antigenic structure different than each of the one or more immunogens identified as one or more boost immunogens. ### Claim 8 (depends on 7) The method of claim 7, further comprising: viii) performing one or more additional binding assays, wherein the binding affinity of the mature bnAb for one or more immunogens is determined, wherein the one or more immunogens comprises the one or more second immunogens identified as the one or more boost immunogens in step (vii), and ix) identifying one or more additional immunogens with enhanced binding affinity for the mature bnAb relative to the one or more second immunogens of step (vii), wherein the one or more additional immunogens with enhanced binding affinity for the mature bnAb is identified as one or more boost immunogens. ### Claim 9 (depends on 7) The method of claim 7 using single cell technology to obtain the pairs of VH and VL chain sequences in step (i). ### Claim 10 (depends on 7) The method of claim 7 using computational methods to infer the sequence of the VH and VL chains of the UA of step (ii). ### Claim 11 (depends on 7) The method of claim 7 wherein the IAs are inferred at each branch point of the clonal lineage of the clonally related B cells. ### Claim 12 (depends on 7) The method of claim 7, wherein the first immunogen identified in step (v) is a different protein than each of the one or more second immunogens identified in step (vii). ### Claim 13 (depends on 8) The method of claim 8, wherein the first immunogen identified in step (v) is a different protein than each of the one or more additional immunogens identified in step (ix), or each of the one or more second immunogens identified in step (vii) is a different protein than each of the one or more additional immunogens identified in step (ix). ### Claim 14 (depends on 13) The method of claim 13, wherein the first immunogen identified in step (v) is a different protein than each of the one or more second immunogens identified in step (vii), wherein the first immunogen identified in step (v) is a different protein than each of the one or more additional immunogens identified in step (ix), and wherein each of the one or more second immunogens identified in step (vii) is a different protein than each of the one or more additional immunogens identified in step (ix). ### Claim 15 (depends on 7) A method of inducing an immune response in a mammal comprising administering to said mammal (a) the first immunogen of claim 7, identified in step (v) as a prime, and (b) the one or more second immunogens of claim 7, identified in step (vii) as a boost, in an amount sufficient to effect said induction. ### Claim 16 (depends on 8, 15) The method of claim 15, further comprising: (c) the one or more additional immunogens of claim 8, identified in step (ix) as a further boost in an amount sufficient to effect said induction. ### Claim 17 (depends on 16) The method of claim 16, wherein the first immunogen for administration as the prime comprises an envelope comprising all of the consecutive amino acids after the signal peptide sequence MRVKETQMNWPNLWKWGTLILGLVIICSA in SEQ ID NO: 2; wherein the one or more second immunogens for administration as a boost is selected from: an envelope comprising all of the amino acids after the signal peptide sequence MRVKETQRSWPNLWKWGTLILGLVIMCNA in SEQ ID NO: 3, an envelope comprising all of the consecutive amino acids after the signal peptide sequence MRVKGIRKNCQQHLWRWGTMLLGILMICSA in SEQ ID NO: 4, or an envelope comprising all of the consecutive amino acids after the signal peptide sequence MRVKGIRKNCQQHLWRWGTMLLGILMICSA in SEQ ID NO: 5; and wherein the one or more additional immunogens for administration as a further boost is selected from an envelope comprising all of the consecutive amino acids after the signal peptide sequence MRVKETQMNWPNLWKWGTLILGLVIICSA in SEQ ID NO: 2, or an envelope comprising all of the amino acids after the signal peptide sequence MRVKETQRSWPNLWKWGTLILGLVIMCNA in SEQ ID NO: 3, in an amount sufficient to effect said induction. ### Claim 18 (depends on 15) The method of claim 15, wherein the first immunogen for administration as the prime is a different protein than each of the one or more second immunogens for administration as the boost. ### Claim 19 (depends on 16) The method of claim 16, wherein the first immunogen for administration as the prime is a different protein than each of the one or more additional immunogens for administration as the further boost, or each of the one or more second immunogens for administration as the boost is a different protein than each of the one or more additional immunogens for administration as the further boost. ### Claim 20 (depends on 19) The method of claim 19, wherein the first immunogen for administration as the prime is a different protein than each of the one or more second immunogens for administration as the boost, wherein the first immunogen for administration as the prime is a different protein than each of the one or more additional immunogens for administration as the further boost, and wherein each of the one or more second immunogens for administration as the boost is a different protein than each of the one or more additional immunogens for administration as the further boost.