Abstract: Disclosed herein are isolated rubella viral vector constructs that include a rubella non-structural protein open reading frame (ORF) without an in-frame deletion, a rubella structural protein ORF, and a heterologous antigenic insert. In one example, the heterologous antigenic insert is positioned within the rubella structural protein ORF. In some examples, the heterologous antigenic insert is positioned in the rubella structural protein ORF in between a gene encoding structural protein E2 and a gene encoding structural protein E1. Exemplary antigenic inserts include HIV, SIV, RSV or hepatitis B surface antigens. In some examples, the HIV antigenic insert is a Gag antigenic insert, a gp41 antigenic insert or a gp120 antigenic insert. Also disclosed are uses of the isolated rubella viral vector, such as to induce an immune response to a particular virus, such as HIV-1, testing sensitivity to neutralizing antibodies, or screening antiviral drugs (such as protease inhibitors).

Abstract: Disclosed herein are isolated immunogens including variant hepatitis B surface antigens (HBsAgs). In an example, a variant HBsAg includes a HBsAg with one or more transmembrane domains of the HBsAg replaced with a gp41 antigenic insert. The antigenic insert can include an antigenic polypeptide fragment of gp41 including the membrane proximal region of gp41 and a transmembrane membrane region of gp41. The replacement of a membrane spanning domain of HBsAg with a membrane spanning domain of gp41 anchors gp41 into HBsAg in virtually the identical orientation as on HIV virions and correctly orients the nearby MPR on the lipid layer. Thus, the disclosed variant HBsAgs display the neutralization-sensitive MPR in association with a lipid layer, while presenting it at the most immunogenic site on HBsAg. Also disclosed are uses of these variant HBsAgs, and nucleic acids encoding variant HBsAgs, such as to induce an immune response to HIV-1.

Abstract: Disclosed herein are isolated immunogens including variant gp120 polypeptides. In an example, a variant gp120 polypeptide includes a deletion of at least 8 consecutive residues of the fourth conserved loop (C4) between residues 419 and 434 of gp120 according to HXB2 numbering. Also provided are isolated nucleic acid molecules encoding the disclosed isolated immunogens. In an example, an isolated nucleic acid molecule further includes a nucleic acid molecule encoding a hepatitis B surface antigen or a variant thereof. Compositions including the isolated immunogens including variant gp120 polypeptides are also disclosed. In some examples, a composition further includes a carrier protein, such as a hepatitis B surface antigen or a variant thereof (natural or recombinant). Viral-like particles are also provided including any of the disclosed isolated immunogens or compositions.

Abstract: Disclosed herein are isolated rubella viral vector constructs that include a rubella non-structural protein open reading frame (ORF) with an in-frame deletion, a rubella structural protein ORF, and a heterologous antigenic insert. In one example, the in-frame deletion within the rubella non-structural protein ORF is an in-frame deletion between two NotI restriction enzyme sites. In some examples, the heterologous antigenic insert is positioned within the rubella non-structural protein ORF. In other examples, the heterologous antigenic insert is positioned within the rubella structural protein ORF. Exemplary antigenic inserts include a Gag antigenic insert, a gp41 antigenic insert or a gp120 antigenic insert. Also disclosed are uses of the isolated rubella viral vector, such as to induce an immune response to HIV-1, testing sensitivity to neutralizing antibodies, or screening antiviral drugs (such as protease inhibitors).

Abstract: Disclosed herein are isolated immunogens including variant hepatitis B surface antigens (HBsAgs). In an example, a variant HBsAg includes a HBsAg with one or more transmembrane domains of the HBsAg replaced with a gp41 antigenic insert. The antigenic insert can include an antigenic polypeptide fragment of gp41 including the membrane proximal region of gp41 and a transmembrane membrane region of gp41. The replacement of a membrane spanning domain of HBsAg with a membrane spanning domain of gp41 anchors gp41 into HBsAg in virtually the identical orientation as on HIV virions and correctly orients the nearby MPR on the lipid layer. Thus, the disclosed variant HBsAgs display the neutralization-sensitive MPR in association with a lipid layer, while presenting it at the most immunogenic site on HBsAg. Also disclosed are uses of these variant HBsAgs, and nucleic acids encoding variant HBsAgs, such as to induce an immune response to HIV-1.

Abstract: Disclosed herein are isolated immunogens including variant hepatitis B surface antigens (HBsAgs). In an example, a variant HBsAg includes a HBsAg with one or more transmembrane domains of the HBsAg replaced with a gp41 antigenic insert. The antigenic insert can include an antigenic polypeptide fragment of gp41 including the membrane proximal region of gp41 and a transmembrane membrane region of gp41. The replacement of a membrane spanning domain of HBsAg with a membrane spanning domain of gp41 anchors gp41 into HBsAg in virtually the identical orientation as on HIV virions and correctly orients the nearby MPR on the lipid layer. Thus, the disclosed variant HBsAgs display the neutralization-sensitive MPR in association with a lipid layer, while presenting it at the most immunogenic site on HBsAg. Also disclosed are uses of these variant HBsAgs, and nucleic acids encoding variant HBsAgs, such as to induce an immune response to HIV-1.

Abstract: Disclosed herein are isolated rubella viral vector constructs that include a rubella non-structural protein open reading frame (ORF) without an in-frame deletion, a rubella structural protein ORF, and a heterologous antigenic insert. In one example, the heterologous antigenic insert is positioned within the rubella structural protein ORF. In some examples, the heterologous antigenic insert is positioned in the rubella structural protein ORF in between a gene encoding structural protein E2 and a gene encoding structural protein E1. Exemplary antigenic inserts include HIV, SIV, RSV or hepatitis B surface antigens. In some examples, the HIV antigenic insert is a Gag antigenic insert, a gp41 antigenic insert or a gp120 antigenic insert. Also disclosed are uses of the isolated rubella viral vector, such as to induce an immune response to a particular virus, such as HIV-1, testing sensitivity to neutralizing antibodies, or screening antiviral drugs (such as protease inhibitors).

Abstract: Disclosed herein are isolated immunogens including variant gp120 polypeptides. In an example, a variant gp120 polypeptide includes a deletion of at least 8 consecutive residues of the fourth conserved loop (C4) between residues 419 and 434 of gp120 according to HXB2 numbering. Also provided are isolated nucleic acid molecules encoding the disclosed isolated immunogens. In an example, an isolated nucleic acid molecule further includes a nucleic acid molecule encoding a hepatitis B surface antigen or a variant thereof. Compositions including the isolated immunogens including variant gp120 polypeptides are also disclosed. In some examples, a composition further includes a carrier protein, such as a hepatitis B surface antigen or a variant thereof (natural or recombinant). Viral-like particles are also provided including any of the disclosed isolated immunogens or compositions.

Abstract: Disclosed herein are isolated immunogens including variant gp120 polypeptides. In an example, a variant gp120 polypeptide includes a deletion of at least 8 consecutive residues of the fourth conserved loop (C4) between residues 419 and 434 of gp120 according to HXB2 numbering. Also provided are isolated nucleic acid molecules encoding the disclosed isolated immunogens. In an example, an isolated nucleic acid molecule further includes a nucleic acid molecule encoding a hepatitis B surface antigen or a variant thereof. Compositions including the isolated immunogens including variant gp120 polypeptides are also disclosed. In some examples, a composition further includes a carrier protein, such as a hepatitis B surface antigen or a variant thereof (natural or recombinant). Viral-like particles are also provided including any of the disclosed isolated immunogens or compositions.

Abstract: Disclosed herein are isolated rubella viral vector constructs that include a rubella non-structural protein open reading frame (ORF) with an in-frame deletion, a rubella structural protein ORF, and a heterologous antigenic insert. In one example, the in-frame deletion within the rubella non-structural protein ORF is an in-frame deletion between two NotI restriction enzyme sites. In some examples, the heterologous antigenic insert is positioned within the rubella non-structural protein ORF. In other examples, the heterologous antigenic insert is positioned within the rubella structural protein ORF. Exemplary antigenic inserts include a Gag antigenic insert, a gp41 antigenic insert or a gp120 antigenic insert. Also disclosed are uses of the isolated rubella viral vector, such as to induce an immune response to HIV-1, testing sensitivity to neutralizing antibodies, or screening antiviral drugs (such as protease inhibitors).

Abstract: Disclosed herein are isolated immunogens including variant hepatitis B surface antigens (HBsAgs). In an example, a variant HBsAg includes a HBsAg with one or more transmembrane domains of the HBsAg replaced with a gp41 antigenic insert. The antigenic insert can include an antigenic polypeptide fragment of gp41 including the membrane proximal region of gp41 and a transmembrane membrane region of gp41. The replacement of a membrane spanning domain of HBsAg with a membrane spanning domain of gp41 anchors gp41 into HBsAg in virtually the identical orientation as on HIV virions and correctly orients the nearby MPR on the lipid layer. Thus, the disclosed variant HBsAgs display the neutralization-sensitive MPR in association with a lipid layer, while presenting it at the most immunogenic site on HBsAg. Also disclosed are uses of these variant HBsAgs, and nucleic acids encoding variant HBsAgs, such as to induce an immune response to HIV-1.

Abstract: Disclosed herein are isolated immunogens including variant gp120 polypeptides. In an example, a variant gp120 polypeptide includes a deletion of at least 8 consecutive residues of the fourth conserved loop (C4) between residues 419 and 434 of gp120 according to HXB2 numbering. Also provided are isolated nucleic acid molecules encoding the disclosed isolated immunogens. In an example, an isolated nucleic acid molecule further includes a nucleic acid molecule encoding a hepatitis B surface antigen or a variant thereof. Compositions including the isolated immunogens including variant gp120 polypeptides are also disclosed. In some examples, a composition further includes a carrier protein, such as a hepatitis B surface antigen or a variant thereof (natural or recombinant). Viral-like particles are also provided including any of the disclosed isolated immunogens or compositions.

Abstract: Recombinant HBsAg-gp120 has been used to present approximately amino acids 1-500 gp120. However, this presentation of gp120 in this form has not successfully been used to produce neutralizing antibodies. The use of the immunogenic Hepatitis B surface antigen (HBsAg) particulate platform to array specific epitopes from the conserved, neutralization-sensitive membrane proximal region (MPR) of HIV-1, and the use of these monomeric fusion proteins, polymeric forms of these fusion proteins, and nucleic acids encoding these fusion proteins to induce an immune response to HIV-1 are disclosed.