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Volume 17, Number 4—April 2011


Hepatitis A Virus Vaccine Escape Variants and Potential New Serotype Emergence

Unai Pérez-Sautu1, M. Isabel Costafreda1, Joan Caylà, Cecilia Tortajada, Josep Lite, Albert Bosch, and Rosa M. PintóComments to Author 
Author affiliations: Author affiliations: University of Barcelona, Barcelona, Spain (U. Pérez-Sautu, M.I. Costafreda, A. Bosch, R.M. Pintó); Public Health Agency of Barcelona, Barcelona (J. Caylà, C. Tortajada); CatLab, Viladecavalls, Spain (J. Lite)

Main Article

Table 2

Neutralization assays of K34C8 MAb-escape variants that showed replacements at the same or very close positions as the mutated positions in the naturally-selected field variants isolated during 2005–2009*†

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).

Main Article

1These authors contributed equally to this article.