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Fig 1.

T cell immunogenic potential for RSV surface proteins based on MHC binding prediction.

(A) T cell immunogenic potential of RSV major surface proteins. T cell epitope density scores for RSV major surface proteins and other pathogen proteins are labeled on a scale bar. Low-scoring proteins are known to engender little to no immunogenicity while higher-scoring proteins are known immunogens. Proteins scoring above +20 on this scale are considered to have significant immunogenic potential. (B) Distribution of RSV T cell immunogenic potential across F and G protein in RSV reference strain A2 and RSV F protein main antigenic sites that are determined in previous studies [26]. Prefusion or post-fusion F protein surface was colored by the antigenic sites and relative immunogenetic potential at each location. Analyses are based on the RSV-A reference sequence.

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Table 1.

Experimentally validated conserved MHC class I epitopes peptides in RSV major surface proteinsa.

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Table 2.

Experimentally validated conserved MHC class II epitopes peptides in RSV major surface proteinsa.

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Fig 2.

Predicted T cell epitope landscapes and genetic evolution of RSV surface proteins.

Filled circles indicate RSV F protein isolates or G protein isolates without duplication. Diamonds indicate G protein isolates with gene duplication. (A) Epitope landscapes of RSV major surface proteins are built with MHC class I and class II epitope content comparison across different strains. T cell immunity clusters are determined with k-means method and are used to color the sequenced isolates in the following panels. (B) The corresponding time-scaled phylogenies are reconstructed with the Maximum Likelihood (ML) approach. (C) T cell epitope immune distance and (D) genetic hamming distance from the estimated TMRCA are plotted against the isolated time of each sequence.

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Fig 3.

Evaluation of previously used RSV vaccine candidate strains with T cell epitope content of circulating strains.

RSV-A and RSV-B major surface protein sequences are subsampled and then grouped by isolation year and 6 isolated WHO regions. African Region (AFRO), Region of the Americas (PAHO), South-East Asia Region (SEARO), European Region (EURO), Eastern Mediterranean Region (EMRO) and Western Pacific Region (WPRO). The proportion of cross-conserved T cell epitope content between live attenuated strains (CP248 or CP52) and wild circulating strains are displayed as radar plots.

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