Poxvirus vectors encoding HIV antigens, and methods of use thereof

Inventors

Wegmann, Frank • Langedijk, Johannes Petrus Maria • Custers, Jerôme Hubertina Henricus Victor • BOCKSTAL, Viki • Kalla, Markus

Assignees

Bavarian Nordic AS • Janssen Vaccines and Prevention BV

Abstract

Poxvirus vectors encoding a synthetic HIV envelope antigen and other HIV antigens, as well as compositions containing such poxvirus vectors and uses of such poxvirus vectors as vaccines to provide improved immunity against HIV, are provided. Also provided are vaccine combinations containing the disclosed poxvirus vectors, adenovirus vectors encoding one or more HIV antigens, and one or more isolated HIV antigenic polypeptides, and methods of using the vaccine combinations to provide improved immunity against HIV.

Core Innovation

The invention relates to inducing an immune response against human immunodeficiency virus (HIV) in a subject by administering a first vaccine and a second vaccine as a prime-boost regimen, where the steps are conducted in either order. The first vaccine comprises one or more recombinant adenovirus vectors encoding HIV antigens comprising amino acid sequences of SEQ ID NOs: 1-5, 18, 28, and 29, together with a carrier. The second vaccine comprises a poxvirus vector carrying nucleic acid encoding multiple distinct HIV antigens including a first HIV envelope (Env) antigen comprising SEQ ID NO: 18, a second Env antigen different from the first, and two different HIV Gag antigens and two different HIV Pol antigens.

The poxvirus component includes poxvirus vector encoding specified combinations of Env antigens and Gag/Pol antigen types, with the Env including SEQ ID NO: 18 and a second Env antigen different from the first. The described approach is implemented through named vector platforms including Modified Vaccinia virus Ankara (MVA) and MVA-BN for the poxvirus vaccine, and recombinant adenovirus 26 (rAd26) for the adenovirus vaccine. The encoded antigen set includes a synthetic HIV envelope protein comprising SEQ ID NO: 18 and further antigens comprising SEQ ID NOs: 5, 28, and 29, including HIV Gag-Pol fusion antigens.

The platform is further defined by optional inclusion of isolated HIV gp140 proteins having specified amino acid spans of SEQ ID NO: 7 (amino acids 30-708) and SEQ ID NO: 36 (amino acids 30-724), and by inclusion of an aluminum phosphate adjuvant. The documentation describes synthetic HIV Env variants encoded by nucleic acids in the vectors and reports improved cell-surface expression and genetic stability compared with a prior mos2Env construct, together with immunogenicity demonstrated in prime-boost regimens using MVA-BN and/or Ad26 vector combinations.

Claims Coverage

The document includes three independent claims that cover prime-boost HIV immune response induction using recombinant adenovirus vectors together with poxvirus vectors, where the prime and boost steps can be performed in either order. Across the independent claims, the main inventive coverage comprises vector-by-antigen mapping for adenovirus and poxvirus delivery and defined antigen sequence requirements, with additional optional components in one claim.

Across the independent claims, the coverage centers on inducing an HIV immune response using an adenovirus vector vaccine and a poxvirus vector vaccine in a prime-boost regimen performed in either order, together with defined antigen content using synthetic HIV Env including SEQ ID NO: 18 and additional Env and two different Gag/Pol antigens, including HIV Gag-Pol fusion antigens with SEQ ID NOs: 28 and 29; one claim further includes optional isolated gp140 proteins and an aluminum phosphate adjuvant.

Stated Advantages

Documented Applications