Methods for inducing an immune response against Human Immunodeficiency Virus (HIV) in HIV-infected subjects undergoing antiretroviral therapy (ART) are described. The methods involve initial administration of an adenovirus vector vaccine and subsequent administration of a poxvirus vector vaccine, followed by administration of anti-HIV broadly neutralizing antibodies (bNAb).

A polypeptide mimicking epitope of glycoprotein gp120 of HIV-1 virus that is recognized by a paratope of broadly neutralizing antibody VRC01 and has the length up to 100 amino acid residues and contains an amino acid sequence:

TABLE-US-00001 (SEQ ID NO. 1): X.sup.1YKNX.sup.2INX.sup.3AX.sup.4X.sup.5VX.sup.6X.sup.7VKRX.sup.8IDX.sup.9ILAX.sup.10LP X.sup.1 is selected from amino acids A, N, R; X.sup.2 is selected from amino acids A, R, D; X.sup.3 is selected from amino acids R, V, P; X.sup.4 is selected from amino acids V, L, S; X.sup.5 is selected from amino acids T, G, R; X.sup.6 is selected from amino acids G, T; X.sup.7 is selected from amino acids L, A; X.sup.8 is selected from amino acids V, I; X.sup.9 is selected from amino acids G, A, R; X.sup.10 is selected from amino acids R, A, G;
with a directly attached alpha-helical structure at the N-terminus or C-terminus is disclosed.

A polypeptide mimicking epitope of glycoprotein gp120 of HIV-1 virus that is recognized by a paratope of broadly neutralizing antibody VRC01 and has the length up to 100 amino acid residues and contains an amino acid sequence:

TABLE-US-00001 (SEQ ID NO. 1): X.sup.1YKNX.sup.2INX.sup.3AX.sup.4X.sup.5VX.sup.6X.sup.7VKRX.sup.8IDX.sup.9ILAX.sup.10LP X.sup.1 is selected from amino acids A, N, R; X.sup.2 is selected from amino acids A, R, D; X.sup.3 is selected from amino acids R, V, P; X.sup.4 is selected from amino acids V, L, S; X.sup.5 is selected from amino acids T, G, R; X.sup.6 is selected from amino acids G, T; X.sup.7 is selected from amino acids L, A; X.sup.8 is selected from amino acids V, I; X.sup.9 is selected from amino acids G, A, R; X.sup.10 is selected from amino acids R, A, G;
with a directly attached alpha-helical structure at the N-terminus or C-terminus is disclosed.

The present disclosure provides compounds of Formula (I) or pharmaceutically acceptable salts thereof: (I) wherein, R1 to R6 and X are defined herein. Also provided are pharmaceutical compositions comprising these compounds, methods for treating Human Immunodeficiency Virus (HIV-1) in a subject in need thereof using these compounds or pharmaceutical compositions, and methods for stabilizing the state-1 conformation of the HIV-1 envelope glycoproteins using these compounds or pharmaceutical compositions.

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The present application relates to method of vaccinating a subject against infection by an enveloped virus. The method includes providing a compound of the Formula (I) as described herein, and contacting the compound of Formula (I) with an isolated enveloped virus, having a membrane, to inactivate the membrane of the isolated enveloped virus. The subject is then treated with the enveloped virus having an inactivated membrane to vaccinate the subject against the enveloped virus. Further disclosed is an ex vivo vaccine composition including the compound of Formula (I) and an enveloped virus.

The present application relates to method of vaccinating a subject against infection by an enveloped virus. The method includes providing a compound of the Formula (I) as described herein, and contacting the compound of Formula (I) with an isolated enveloped virus, having a membrane, to inactivate the membrane of the isolated enveloped virus. The subject is then treated with the enveloped virus having an inactivated membrane to vaccinate the subject against the enveloped virus. Further disclosed is an ex vivo vaccine composition including the compound of Formula (I) and an enveloped virus.

Methods of inducing an immune response against human immunodeficiency virus (HIV) are described. In particular, methods of inducing an immune response against HIV by co-locally administering an immunogenically effective amount of an isolated HIV envelope (Env) polypeptide and an immunogenically effective amount of an adenovirus vector encoding an HIV antigen, e.g., Env antigen are described. The isolated HIV Env polypeptide and adenovirus vector can be administered in a single composition or in separate compositions, in which the composition or compositions do not contain an adjuvant.

Methods of inducing an immune response against human immunodeficiency virus (HIV) are described. In particular, methods of inducing an immune response against HIV by co-locally administering an immunogenically effective amount of an isolated HIV envelope (Env) polypeptide and an immunogenically effective amount of an adenovirus vector encoding an HIV antigen, e.g., Env antigen are described. The isolated HIV Env polypeptide and adenovirus vector can be administered in a single composition or in separate compositions, in which the composition or compositions do not contain an adjuvant.

Provided is a recombinant BCG employing a pMyong2 vector system to express HIV-1 p24 and a use thereof as a HIV-1 vaccine. rBCG-pMyong2-p24, which is a pMyong2 vector system, was found to induce the upregulation of HIV-1 p24 gag expression in rBCG and infected antigen-presenting cells (APC) and to induce improved p24-specific immune responses in vaccinated mice, compared to rBCG-pAL-p24 in a pAL5000 derived vector system. rBCG-pMyong2-p24 was identified to exhibit a higher p24-specific Ab production level than rSmeg-pMyong2-p24 in the same pMyong2 vector system. Therefore, the recombinant BCG employing rBCG-pMyong2-p24 to express HIV-1 p24 according to the present invention is identified to elicit enhanced immune responses to HIV-1 infection in mouse model systems and thus can be expected to be used as a prime vaccine in the heterologous prime-boost vaccination strategy against HIV-1 infection.

Provided is a recombinant BCG employing a pMyong2 vector system to express HIV-1 p24 and a use thereof as a HIV-1 vaccine. rBCG-pMyong2-p24, which is a pMyong2 vector system, was found to induce the upregulation of HIV-1 p24 gag expression in rBCG and infected antigen-presenting cells (APC) and to induce improved p24-specific immune responses in vaccinated mice, compared to rBCG-pAL-p24 in a pAL5000 derived vector system. rBCG-pMyong2-p24 was identified to exhibit a higher p24-specific Ab production level than rSmeg-pMyong2-p24 in the same pMyong2 vector system. Therefore, the recombinant BCG employing rBCG-pMyong2-p24 to express HIV-1 p24 according to the present invention is identified to elicit enhanced immune responses to HIV-1 infection in mouse model systems and thus can be expected to be used as a prime vaccine in the heterologous prime-boost vaccination strategy against HIV-1 infection.