The invention relates to germline-targeting designs, stabilization designs, and/or combinations thereof, of proteins designed with modified surfaces helpful for immunization regimens, other protein modifications and/or development of nanoparticles, methods of making and using the same, and to (a) germline-targeting priming or boosting/shepherding immunogens to initiate or guide maturation of VRC01-class responses (b) PCT64/PG9-germline-targeting designs (c) BG18-germline-targeting designs or boosting/shepherding immunogens to initiate or guide maturation of BG18-like responses, and/or (d) trimer stabilization and presentation in a membrane-bound format.

The present invention relates to methods and compositions for the stimulation of immune responses. Specifically, the present invention provides methods of inducing an immune response to human immunodeficiency virus (HIV) in a subject (e.g., a human subject) and compositions useful in such methods (e.g., a nanoemulsion comprising HIV or antigenic portion thereof).

The present invention provides methods for producing HIV-1 nanoparticle vaccines with enhanced immunogenicity. The methods entail (1) enzymatic digestion of glycan chain on the surface of a self-assembling nanoparticle vaccine displaying an HIV-1 Env derived trimer immunogen, or (2) expression of an HIV-1 nanoparticle construct in an expression system lacking normal glycosylation function for human proteins. Also provided in the invention are HIV-1 nanoparticle vaccines produced with the described methods. The invention further provides methods of using the HIV-1 nanoparticle vaccine compositions described herein in various therapeutic applications, e.g., for preventing or treating viral infections.

The disclosure relates to nucleic acids mosaic clade M HIV-1 Env polypeptides and to compositions and vectors comprising same. The nucleic acids are suitable for use in inducing an immune response to HIV-1 in a human.

The invention provides structurally constrained viral peptides for use as therapeutic and vaccination agents, and for the production of antibodies for use in a number of applications including as therapeutic agents. The invention further provides methods and kits for use of the structurally constrained peptides and antibodies of the instant invention. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.

The invention is directed to virus-like particles (VLPs) of an RNA bacteriophage that (a) comprises a coat polypeptide of said phage modified by insertion of a heterologous peptide that is displayed on said VLP and (b) encapsidates said bacteriophage mRNA as well as populations of these VLPs, and their uses. The invention is further directed to VLPs that encapsidate heterologous substances, as well as populations of these VLPs and their uses.

The present invention relates to an immunogenic composition comprising an antigenic peptide of formula (I) below: Nt-S-X1-X2-X3-K-X4-Ct (I) [SEQ ID No 1], wherein —Nt consists of a peptide having from 0 to 50 amino acids in length, —Ct consists of a peptide having from 0 to 50 amino acids in length, —each of X1 to X4 consists of an amino acid residue, wherein: —(i) X1 means the specific amino acid W or (ii) X1 means any amino acid residue excepted W, —(i) X2 means the specific amino acid S or (ii) X2 means any amino acid residue excepted S, —(i) X3 means the specific amino acid N or (ii) X3 means any amino acid residue excepted N, —(i) X4 means the specific amino acid S or (ii) X4 means any amino acid residue excepted S, with the proviso that —three out of the four amino acid residues X1, X2, X3 and X4 mean the specific amino acid defined in their respective meaning (i) above, and —the remaining amino acid residue among X1 to X4 means any amino acid residue excepted the specific amino acid residue defined in its meaning (i), for preventing and/or treating an infection of an individual with an HIV-1 virus.

This invention features polypeptides, variants thereof, and fragments thereof useful in eliciting an immune response (e.g., neutralizing antibodies) against a broad spectrum of HIV-1 isolates. The polypeptides, variants, and fragments include a portion of the gp120 V2 domain of HIV-1. The polypeptides, variants, and fragments display an epitope that is recognized by at least one antibody which neutralizes at least one HIV-1 primary isolate. This invention also features nucleic acid sequences encoding those polypeptides. In addition, the invention provides methods of screening for inhibitors of HIV-1 entry into cells, as well as methods of treatment using the inhibitors.

Disclosed are chimeric polypeptides based on viral membrane fusion proteins. More particularly, the present invention discloses chimeric polypeptides that comprise a virion surface exposed portion of a viral fusion protein and a heterologous structure-stabilizing moiety, and to complexes of those chimeric polypeptides. The present invention also discloses the use of these complexes in compositions and methods for eliciting an immune response to a fusion protein of an enveloped virus, or complex of the fusion protein, and/or for treating or preventing an enveloped virus infection. The present invention further discloses the use of the heterologous structure-stabilizing moiety for oligomerizing heterologous molecules of interest.

Therapeutic compositions and methods for treating HIV including identification and manipulation of particular domains associated with immunogenicity.