Selection and characterization of human respiratory syncytial virus escape mutants resistant to a polyclonal antiserum raised against the F protein

Tomé, Lorena; Frabasile, Sandra; Candia, Claudia; Pittini, Álvaro; Farina, Natalia; Melero, José A.; Arbiza, Juan

doi:10.1007/s00705-012-1274-2

Cited by 8 publications

(6 citation statements)

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“…It is worth stressing that frequently the same mutation could be repeatedly selected with different antibodies (e.g., K272N isolated with mAbs 151, 1200, 47F and palivizumab). Occasionally, more than one amino acid change was selected at the same position (e.g., N262S or N262Y) and one of the changes (N268I) was also selected after passing the virus in the presence of a polyclonal rabbit antiserum raised against purified F protein (Tome et al 2012). These findings probably reflect the dominance of certain epitopes and the propensity of the F protein to incorporate certain mutations but not others.…”

Section: Protective Antigensmentioning

confidence: 99%

Influence of Respiratory Syncytial Virus Strain Differences on Pathogenesis and Immunity

Melero

Moore

2013

Current Topics in Microbiology and Immunology

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Molecular epidemiology studies have provided convincing evidence of antigenic and sequence variability among respiratory syncytial virus (RSV) isolates. Circulating viruses have been classified into two antigenic groups (A and B) that correlate with well-delineated genetic groups. Most sequence and antigenic differences (both inter- and intra-groups) accumulate in two hypervariable segments of the G protein gene. Sequences of the G gene have been used for phylogenetic analyses. These studies have shown a worldwide distribution of RSV strains with both local and global replacement of dominant viruses with time. Although data are still limited, there is evidence that strain variation may contribute to differences in pathogenicity. In addition, there is some but limited evidence that RSV variation may be, at least partially, immune (antibody) driven. However, there is the paradox in RSV that, in contrast to other viruses (e.g., influenza viruses) the epitopes recognized by the most effective RSV-neutralizing antibodies are highly conserved. In contrast, antibodies that recognize strain-specific epitopes are poorly neutralizing. It is likely that this apparent contradiction is due to the lack of a comprehensive knowledge of the duration and specificities of the human antibody response against RSV antigens. Since there are some data supporting a group- (or clade-) specific antibody response after a primary infection in humans, it may be wise to consider the incorporation of strains representative of groups A and B (or their antigens) in future RSV vaccine development.

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Section: Protective Antigensmentioning

confidence: 99%

Influence of Respiratory Syncytial Virus Strain Differences on Pathogenesis and Immunity

Melero

Moore

2013

Current Topics in Microbiology and Immunology

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“…(iii) The N268I mutation, which is frequently selected with monoclonal and polyclonal antibodies (48), had a minimal impact on neutralization by Nb017 and ALX-0171, despite being selected in this study with Nb017.…”

Section: Resultsmentioning

confidence: 90%

“…At the end of the selection process a single viral plaque was isolated from each culture to avoid mixture of viruses and ensure homogeneity of the mutant stock, and the F protein gene was sequenced, as described previously (48). The amino acid changes in each mutant are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

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Trivalency of a Nanobody Specific for the Human Respiratory Syncytial Virus Fusion Glycoprotein Drastically Enhances Virus Neutralization and Impacts Escape Mutant Selection

Palomo

Más

Detalle

et al. 2016

Antimicrob Agents Chemother

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ALX-0171 is a trivalent Nanobody derived from monovalent Nb017 that binds to antigenic site II of the human respiratory syncytial virus (hRSV) fusion (F) glycoprotein. ALX-0171 is about 6,000 to 10,000 times more potent than Nb017 in neutralization tests with strains of hRSV antigenic groups A and B. To explore the effect of this enhanced neutralization on escape mutant selection, viruses resistant to either ALX-0171 or Nb017 were isolated after serial passage of the hRSV Long strain in the presence of suboptimal concentrations of the respective Nanobodies. Resistant viruses emerged notably faster with Nb017 than with ALX-0171 and in both cases contained amino acid changes in antigenic site II of hRSV F. Detailed binding and neutralization analyses of these escape mutants as well as previously described mutants resistant to certain monoclonal antibodies (MAbs) offered a comprehensive description of site II mutations which are relevant for neutralization by MAbs and Nanobodies. Notably, ALX-0171 showed a sizeable neutralization potency with most escape mutants, even with some of those selected with the Nanobody, and these findings make ALX-0171 an attractive antiviral for treatment of hRSV infections.

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“…As quasiespécies naturais de vírus de RNA permitem a emergência rápida de vírus mutantes que escapam da pressão imune do hospedeiro frente a este monoclonal (Moraes et al, 2015). Trabalhos prévios demonstraram que mutações nos aminoácidos S268I, K272Q, K272E, S275L e N276S já existem na população e podem propiciar pacientes com recidivas (Zhu et al, 2011;Papenburg et al, 2012;Tomé et al, 2012;Oliveira et al, 2015). A subunidade F1 é relativamente bem conservada, sendo sua função comprometida mediante estas deleções ou substituições de aminoácidos (Collins et al, 2001, Tomé et al, 2012.…”

Section: Epidemiologia E Patogeniaunclassified

Avaliação da susceptibilidade de mutantes de escape do vírus sincicial respiratório frente ao Palivizumab pelo método de microneutralização <i>in vitro</i>.

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Selection and characterization of human respiratory syncytial virus escape mutants resistant to a polyclonal antiserum raised against the F protein

Cited by 8 publications

References 50 publications

Influence of Respiratory Syncytial Virus Strain Differences on Pathogenesis and Immunity

Influence of Respiratory Syncytial Virus Strain Differences on Pathogenesis and Immunity

Trivalency of a Nanobody Specific for the Human Respiratory Syncytial Virus Fusion Glycoprotein Drastically Enhances Virus Neutralization and Impacts Escape Mutant Selection

Avaliação da susceptibilidade de mutantes de escape do vírus sincicial respiratório frente ao Palivizumab pelo método de microneutralização <i>in vitro</i>.

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