HAV Vaccine Escape Variants | CDC EID

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Volume 17, Number 4–April 2011
Dispatch
Hepatitis A Virus Vaccine Escape Variants and Potential New Serotype Emergence
Unai Pérez-Sautu,1 M. Isabel Costafreda,1 Joan Caylà, Cecilia Tortajada, Josep Lite, Albert Bosch, and Rosa M. Pintó

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); and CatLab, Viladecavalls, Spain (J. Lite)

Suggested citation for this article

Abstract
Six hepatitis A virus antigenic variants that likely escaped the protective effect of available vaccines were isolated, mostly from men who have sex with men. The need to complete the proper vaccination schedules is critical, particularly in the immunocompromised population, to prevent the emergence of vaccine-escaping variants.


In areas where hepatitis A has low to moderate endemicity, introduction of the virus occurs through consumption of imported foods, traveling, or through immigration flows (1–3). Men who have sex with men (MSM) comprise a high-risk group for hepatitis A, and several outbreaks affecting this group have been reported across Europe (4). To prevent the spread of infection, since 1999, vaccination programs have been implemented among preadolescents in the Catalonia Autonomous Community of Spain.

Despite some degree of nucleotide heterogeneity at the capsid region of hepatitis A virus (HAV) (5,6), there is not an equivalent degree of amino acid variation (7). HAV replicates as complex dynamic mutant distributions or quasispecies (8) and thus the high degree of conservation of the capsid amino acid sequences among independent strains must be the result of negative selection on newly arising mutants. So far, a single serotype of human HAV has been recognized, which suggests that severe structural constraints occur in the capsid that prevent the more extensive substitutions necessary for the emergence of a new serotype. Indeed, negative selection of replacements affecting residues encoded by rare codons of the capsid surface has been documented, indicating a critical role played by such rare codons (9). Since these residues are located quite near or even at the epitope regions, the need to maintain such rare codons might prevent the emergence of new serotypes (9). We have recently noted that fine-tuning translation kinetics selection, or the right combination of preferred and rare codons in the capsid coding region, is necessary to get regulated ribosome traffic to guarantee the proper capsid folding (10). In this context, it seems quite unlikely that a new serotype will emerge, although the emergence of new variants is not impossible if the virus population is forced through bottleneck conditions such as immune selective pressures. We investigated the presence of antigenic variants among sporadic and outbreak cases of hepatitis A.

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HAV Vaccine Escape Variants | CDC EID



Suggested Citation for this Article
Pérez-Sautu U, Costafreda MI, Caylà J, Tortajada C, Lite J, Bosch A, et al. Hepatitis A virus vaccine escape variants and potential new serotype emergence. Emerg Infect Dis [serial on the Internet]. 2011 Apr [date cited].
http://www.cdc.gov/EID/content/17/4/734.htm


DOI: 10.3201/eid1704.101169


Comments to the Authors
Please use the form below to submit correspondence to the authors or contact them at the following address:

Rosa M. Pintó, Department of Microbiology, School of Biology, Diagonal 645, 08028, Barcelona, Spain; email: rpinto@ub.edu