Circulating rotavirus strains in children with acute gastroenteritis in Iran, 1986 to 2023 and their genetic/antigenic divergence compared to approved vaccines strains (Rotarix, RotaTeq, ROTAVAC, ROTASIIL) before mass vaccination: Clues for vaccination policy makers

Abstract

In the present study, first, rotaviruses that caused acute gastroenteritis in children under five years of age during the time before the vaccine was introduced in Iran (1986 to 2023) are reviewed. Subsequently, the antigenic epitopes of the VP7 and VP4/VP8 proteins in circulating rotavirus strains in Iran and that of the vaccine strains were compared and their genetic differences in histo-blood group antigens (HBGAs) and the potential impact on rotavirus infection susceptibility and vaccine efficacy were discussed. Overall data indicate that rotavirus was estimated in about 38.1 % of samples tested. The most common genotypes or combinations were G1 and P[8], or G1P[8]. From 2015 to 2023, there was a decline in the prevalence of G1P[8], with intermittent peaks of genotypes G3P[8] and G9P[8]. The analyses suggested that the monovalent Rotarix vaccine or monovalent vaccines containing the G1P[8] component might be proper in areas with a similar rotavirus genotype pattern and genetic background as the Iranian population where the G1P[8] strain is the most predominant and has the ability to bind to HBGA secretors. While the same concept can be applied to RotaTeq and RotasIIL vaccines, their complex vaccine technology, which involves reassortment, makes them less of a priority. The ROTASIIL vaccine, despite not having the VP4 arm (P[5]) as a suitable protection option, has previously shown the ability to neutralize not only G9-lineage I strains but also other G9-lineages at high titers. Thus, vaccination with the ROTASIIL vaccine may be more effective in Iran compared to RotaTeq. However, considering the rotavirus genotypic pattern, ROTAVAC might not be a good choice for Iran. Overall, the findings of this study provide valuable insights into the prevalence of rotavirus strains and the potential effectiveness of different vaccines in the Iranian and similar populations.

Keywords: Genotype; Rotavirus; VP4; VP7; Vaccine; lineage.

Fig. 1

Phylogenetic analysis based on the nucleotide sequence of the VP7 (G1-G4, G9, and G12) and VP4/VP8 genes (P[8], P[4], and P[6]. The phylogenetic trees were constructed based on nucleotide sequence of VP7 G1 (A), G2 (B), G3 (C), G4 (D), G9 (E), G12 (F), and VP4/VP8 P[8] (G), P[4] (H), P[6] (I). The trees were constructed through the maximum likelihood method (MLM), using the Kimura 2-parameter model. Trees were statistically supported by bootstrapping with 1000 replicates. Only bootstrap values greater than 50 % are presented. The scale bar represents 0.1 (G12, P[4]), 0.05 (G3), 0.02 (G1, G2, G4, G9, P[8], P[6]) genetic distance. The sequences of rotavirus strains identified in this study are indicated by the strain names with green squares. The reference strains are indicated by the strain names.

Fig. 1

Phylogenetic analysis based on the nucleotide sequence of the VP7 (G1-G4, G9, and G12) and VP4/VP8 genes (P[8], P[4], and P[6]. The phylogenetic trees were constructed based on nucleotide sequence of VP7 G1 (A), G2 (B), G3 (C), G4 (D), G9 (E), G12 (F), and VP4/VP8 P[8] (G), P[4] (H), P[6] (I). The trees were constructed through the maximum likelihood method (MLM), using the Kimura 2-parameter model. Trees were statistically supported by bootstrapping with 1000 replicates. Only bootstrap values greater than 50 % are presented. The scale bar represents 0.1 (G12, P[4]), 0.05 (G3), 0.02 (G1, G2, G4, G9, P[8], P[6]) genetic distance. The sequences of rotavirus strains identified in this study are indicated by the strain names with green squares. The reference strains are indicated by the strain names.

Fig. 2

Alignment of the antigenic epitopes in VP7 between Rotarix, RotaTeq, ROTAVAC, and ROTASIIL vaccines and strains circulating in Iran. Alignment of the antigenic epitopes in VP7 of the rotavirus strains circulating in Iran with Rotarix, RotaTeq, ROTASIIL, and ROTAVAC. Residues that differ from Rotarix, RotaTeq, ROTASIIL, and ROTAVAC are highlighted in red; residues similar to Rotarix are shaded in pea green, those similar to Rotateq in blue, and those similar to ROTASIIL in teal (A). Surface representation cartoon of the VP7 monomer and trimer (PDB 3FMG). Antigenic epitopes are colored yellow (7–1a), pink (7–1b), and green (7–2). Substitutions relevant to the vaccine strains are depicted in blue (B).

Fig. 3

Alignment of the antigenic epitopes in VP4/VP8* between Rotarix/RotaTeq vaccines and strains circulating in Iran. Alignment of the antigenic epitopes in VP8 between Rotarix and RotaTeq, and strains circulating in Iran. Amino acid residues shaded in pink and green differ from Rotarix and RotaTeq, respectively; amino acid residues highlighted in pink/green differ from both Rotarix and RotaTeq (A). The VP8 core is represented on the surface (PDB KQR). Antigenic epitopes are highlighted in yellow (8‐1), pink (8‐2), orange (8‐3), and green (8‐4). Surface-exposed residues that differ between P[8] strains and vaccine strains are shown in light blue (B).