Reply to Nalin

To the Editor—We thank Dr Nalin for endorsing the idea that evaluation of a single-dose vaccination schedule should be considered in the clinical evaluation of future vaccines and for noting the case of formalin-inactivated hepatitis A virus (HAV) vaccines. We fully agree with Dr Nalin that vaccine-induced effector mechanisms, in addition to antibody levels at the time of exposure, might be relevant to protection against some infectious diseases. It may well be that an anamnestic response induced during the early stages of infection can protect against HAV-induced liver disease, as appears to be the case for hepatitis B [1]. This consideration led us to suggest in our commentary that, in the development of future subunit prophylactic vaccines, it will be important to consider whether sterilizing immunity from initial infection is critical and to determine whether virus-like display is as superior a strategy for inducing memory B-cell responses as it appears to be for inducing durable serum antibody titers.

HAV vaccines exemplify the difficulties in adopting single-dose vaccination programs after licensure. In addition to the demonstration by the cited study of strong short-term (<4 months) protection in an outbreak setting after a single dose, single-dose protection was subsequently evaluated in several trials of varying lengths of up to 11 years and in a large public vaccination program in Argentina [2]. These findings led a World Health Organization Strategic Advisory Group of Experts on Immunization working group in 2012 to conclude that “a 1-dose schedule might be an effective and useful option for immunization programs, but [the group] cautioned that the evidence presented was limited” [3p16]. The current evidence has apparently proven insufficient to convince other national regulatory agencies to adopt single-dose HAV vaccination programs.