Volume 17, Number 4—April 2011
Dispatch
Hepatitis A Virus Vaccine Escape Variants and Potential New Serotype Emergence
Table 2
Mutant (position replaced) | log Nt/N0 vaccine serum (HAVRIX) | log Nt/N0 vaccine serum (Avaxim) | log Nt/N0 convalescent-phase serum (HCS2) | log Nt/N0 MAb K34C8 |
---|---|---|---|---|
C6 (1170) | –0.08 ± 0.14 | –0.08 ± 0.14 | –0.02 ± 0.04 | –0.08 ± 0.14 |
P29 (1187) | –0.70 ± 0.09 | –0.30 ± 0.19 | –0.70 ± 0.07 | –0.37 ± 0.19 |
D23 (1217) | –0.88 ± 0.02 | –0.54 ± 0.01 | –0.61 ± 0.07 | –0.58 ± 0.12 |
HM175/43c | –0.69 ± 0.09 | –0.60 ± 0.05 | –0.65 ± 0.05 | –0.61 ± 0.10 |
*Assays were performed by using vaccine and convalescent-phase serum samples as well as K34C8 MAb. MAb, monoclonal antibody; HAVRIX, HAVRIX vaccine (GlaxoSmithKline, Rixenart, Belgium); Avaxim, Avaxim vaccine (Sanofi-Pasteur, Paris, France).
†Following the model of the hepatitis A virus protomer of Ming Luo (Figure 1). Three neutralization assays were performed with each antivaccine serum sample, the convalescent-phase serum sample, and the MAb K34C8. As controls, neutralization of the D23 H7C27 MAb escape variant (9) as well as that of the HM175/43c wild-type strain, was also measured. The highest dilution showing a log Nt/N0 = –0.60 (75% neutralization) of the wild-type strain was used to test the variants; Nt, the viral titer after neutralization; N0, the initial titer. Neutralization limits were the following: log Nt/N0>–0.26 (<45%) for resistant variants, –0.26>log Nt/N0>–0.60 (45%–75%) for partially resistant variants, and log Nt/N0<–0.60 (>75%) for sensitive variants (9).
References
- Pintó RM, Costafreda MI, Bosch A. Risk assessment in shellfish-borne outbreaks of hepatitis A. Appl Environ Microbiol. 2009;75:7350–5. DOIPubMedGoogle Scholar
- Wheeler C, Vogt TM, Armstrong GL, Vaughan G, Weltman A, Nainan OV, An outbreak of hepatitis A associated with green onions. N Engl J Med. 2005;353:890–7. DOIPubMedGoogle Scholar
- Faber MS, Stark K, Behnke SC, Schreier E, Frank C. Epidemiology of hepatitis A virus infections, Germany, 2007–2008. Emerg Infect Dis. 2009;15:1760–8.PubMedGoogle Scholar
- Stene-Johansen K, Tjon G, Schreier E, Bremer V, Bruisten S, Ngui SL, Molecular epidemiological studies show that hepatitis A virus is endemic among active homosexual men in Europe. J Med Virol. 2007;79:356–65. DOIPubMedGoogle Scholar
- Costa-Mattioli M, Napoli AD, Ferre V, Billaudel S, Perez-Bercoff R, Cristina J. Genetic variability of hepatitis A virus. J Gen Virol. 2003;84:3191–201. DOIPubMedGoogle Scholar
- Robertson BH, Jansen RW, Khanna B, Totsuka A, Nainan OV, Siegl G, Genetic relatedness of hepatitis A virus strains recovered from different geographical regions. J Gen Virol. 1992;73:1365–77. DOIPubMedGoogle Scholar
- Sánchez G, Bosch A, Pintó RM. Genome variability and capsid structural constraints of hepatitis A virus. J Virol. 2003;77:452–9. DOIPubMedGoogle Scholar
- Sánchez G, Bosch A, Gomez-Mariano G, Domingo E, Pintó RM. Evidence for quasispecies distributions in the human hepatitis A virus genome. Virology. 2003;315:34–42. DOIPubMedGoogle Scholar
- Aragonès L, Bosch A, Pintó RM, Hepatitis A. Virus mutant spectra under the selective pressure of monoclonal antibodies: codon usage constraints limit capsid variability. J Virol. 2008;82:1688–700. DOIPubMedGoogle Scholar
- Aragonès L, Guix S, Ribes E, Bosch A, Pintó RM. Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid. PLoS Pathog. 2010;6:e1000797. DOIPubMedGoogle Scholar
- Luo M, Rossmann MG, Palmenberg AC. Prediction of three-dimensional models for foot-and-mouth disease virus and hepatitis a virus. Virology. 1988;166:503–14. DOIPubMedGoogle Scholar
- Ping LH, Lemon SM. Antigenic structure of human hepatitis A virus defined by analysis of escape mutants selected against murine monoclonal antibodies. J Virol. 1992;66:2208–16.PubMedGoogle Scholar
- Sánchez G, Aragonès L, Costafreda MI, Ribes E, Bosch A, Pintó RM. Capsid region involved in hepatitis a virus binding to glycophorin A of the erythrocyte membrane. J Virol. 2004;78:9807–13. DOIPubMedGoogle Scholar
- Weissman S, Feucht C, Moore BA. Response to hepatitis A vaccine in HIV-positive patients. J Viral Hepat. 2006;13:81–6. DOIPubMedGoogle Scholar
- Neilsen GA, Bodsworth NJ, Watts N. Response to hepatitis A vaccination in human immunodeficiency virus-infected and -uninfected homosexual men. J Infect Dis. 1997;176:1064–7. DOIPubMedGoogle Scholar
1These authors contributed equally to this article.