A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection

Abstract

Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries.

Comparison of the safety and immunogenicity of live attenuated and inactivated hepatitis A vaccine in healthy Chinese children aged 18 months to 16 years: results from a randomized, parallel controlled, phase IV study

“…However, after administration of the booster dose of HA-I, the anti-HAV IgG titre was higher than that after one dose of the vaccine, consistent with previous studies showing that the two-dose regimen is more effective than the onedose regimen over a short period [24]. HA-I can induce T-cellmediated immunity more effectively than HA-L [25]; when the body is re-infected with HAV, the levels of the cellular response and some cytokines such as interferon-g, interleukin-2 and interleukin-12 can rapidly and intensively evoke memory immune responses [26]. The booster dose of HA-I can simulate mild natural infection, resulting in significant increases in anti-HAV IgG titres after booster vaccination.…”

Clinical experience with the inactivated hepatitis A vaccine, Avaxim 80U Pediatric

“…In endemic settings, a single HAV vaccine dose induces HAV-specific cellular memory immune responses similar to natural infection that are likely sufficient to ensure protection and natural boosting when exposed to HAV, independently of the circulating antibody levels achieved [56,57]. Indeed, a single dose universal HAV vaccination program for children has been introduced in some countries in Latin America [57]. In Argentina, different vaccines have been used by the government since the program began in 2005, including the pediatric HAV vaccine (Avaxim®80U Pediatric).…”

Modelling the decline and future of hepatitis A transmission in Australia

“…Our results project that a return to an endemic phase in Australia is only possible under a combination of highly pessimistic assumptions regarding the duration of vaccine‐conferred immunity, immunity of future migrants and vaccination patterns. Studies of the duration of hepatitis A vaccine protection are naturally censored by <25 years of data availability but long‐term cohort studies supported by modelling projections report at least 14 years and 25 years of observed evidence, with immune response found to be similar to that induced by a natural infection, inferring lifelong protection by hepatitis A vaccination. Australia continues to see high rates of migration from intermediate‐ and high‐endemicity countries and available data on vaccine uptake suggest that this if anything has increased with time in the period up to 2015.…”

“…We implemented our model as a system of differential equations (equations (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) in Appendix S1) in Matlab R2016b (The Mathworks Inc., Natick, MA, USA).…”

“…While the potential for both person‐to‐person and point‐source transmission make estimating reproduction numbers challenging for hepatitis A, existing estimates suggest that the basic reproduction number ( R 0 ) is probably no higher than 2‐4 in endemic and special risk populations and lower in general populations in countries with strong public health infrastructure in relation to the modes of transmission of hepatitis A. Given the moderate R 0 and the fact that vaccination leads to long‐lasting and effective immunity, local elimination of hepatitis A could be a readily achievable target in such settings.…”