Construction of four double gene substitution human × bovine rotavirus reassortant vaccine candidates: Each bears two outer capsid human rotavirus genes, one encoding P serotype 1A and the other encoding G serotype 1, 2, 3, or 4 specificity

Abstract

Previously, four human x bovine rotavirus reassortant candidate vaccines, each of which derived ten genes from bovine rotavirus UK strain and only the outer capsid protein VP7-gene from human rotavirus strain D (G serotype 1), DS-1 (G serotype 2), P (G serotype 3), or ST3 (G serotype 4), were developed [Midthun et al., (1985): Journal of Virology 53:949-954; (1986): Journal of Clinical Microbiology 24:822-826]. Such human x bovine reassortant vaccines should theoretically provide antigenic coverage for the four epidemiologically most important VP7(G) serotypes 1, 2, 3, and 4. In an attempt to increase the antigenicity of VP7-based human x animal reassortant rotavirus vaccines which derive a single VP7-encoding gene from the human strain and the remaining ten genes from the animal strain, we generated double gene substitution reassortants. This was done by incorporating another protective antigen (VP4) of an epidemiologically important human rotavirus by crossing human rotavirus Wa strain (P serotype 1A), with each of the human x bovine single VP7-gene substitution rotavirus reassortants. In this way four separate double gene substitution rotavirus reassortants were generated. Each of these reassortants bears the VP4-encoding gene from human rotavirus Wa strain, the VP7-encoding gene from human rotavirus strain D, DS-1, P, or ST3, and the remaining nine genes from bovine rotavirus strain UK. The safety, antigenicity, and protective efficacy of individual components as well as combinations of strains are currently under evaluation.

The rotavirus vaccine development pipeline

“…The US National Institutes of Health (NIH) UK-Compton bovine rotavirus vaccine (UK-BRV) is a multivalent bovine-human rotavirus reassortant vaccine comprised of the G6P[5] bovine rotavirus backbone with the VP7 genes from the common human rotavirus strains incorporated as reassortants into the vaccine strains [55]. The human VP7 genes for G1 (strain D), G2 (DS-1), G3 (P) and G4 (ST-3) were established first and this quadrivalent vaccine candidate was evaluated in clinical trials showing robust immune responses to the rotavirus antigens, good safety data and non-interference with the routine childhood vaccines when co-administered [56], [57].…”

Effect of rotavirus genetic diversity on vaccine impact

“…93 3.4.2 | Bovine-human reassortant rotavirus vaccine UK-Compton bovine rotavirus (UK-BRV) is a multivalent bovinehuman rotavirus reassortant vaccine consisting of the G6P [5] backbone of bovine rotavirus with VP7 genes from common human rotavirus strains, that is G1 (strain D), G2 (DS-1), G3 (P) and G4 (ST-3). 94 This quadrivalent vaccine candidate was tested in clinical trials showing strong immune responses to rotavirus antigens, effective safety results and non-interaction with common childhood vaccines when co-administrated. 95,96 These findings led to the global production of the vaccine candidate; and the NIH developed more reassortants to include components for G8 (strain 1290) and G9…”

Homotypic and Heterotypic Serum Isotype–Specific Antibody Responses to Rotavirus Nonstructural Protein 4 and Viral Protein (VP) 4, VP6, and VP7 in Infants Who Received Selected Live Oral Rotavirus Vaccines

“…Rotavirus outer-capsid proteins VP4 and VP7, which determine the P and G serotype specificity, respectively, induce neutralizing antibodies independently and are considered to be critical in protective immunity to rotavirus disease [25,26]. Hence, major serotypes of VP4 (P1A [8]) and/or VP7 (G1, G2, G3, and G4), which are of global epidemiological importance, have been included in candidate rotavirus vaccines [4,[27][28][29][30][31]. However, the extent of homotypic and heterotypic VP4-or VP7-specific IgA antibody responses in infants and young children who received such vaccines has not been fully delineated.…”