Live Oral Adenovirus Type 4 and Type 7 Vaccine Induces Durable Antibody Response

Abstract

Human adenoviruses (AdV) are mostly associated with minimal pathology. However, more severe respiratory tract infections and acute respiratory diseases, most often caused by AdV-4 and AdV-7, have been reported. The only licensed vaccine in the United States, live oral AdV-4 and AdV-7 vaccine, is indicated for use in the military, nearly exclusively in recruit populations. The excellent safety profile and prominent antibody response of the vaccine is well established by placebo-controlled clinical trials, while, long-term immunity of vaccination has not been studied. Serum samples collected over 6 years from subjects co-administered live oral AdV-4 and AdV-7 vaccine in 2011 were evaluated to determine the duration of the antibody response. Group geometric mean titers (GMT) at 6 years post vaccination compared to previous years evaluated were not significantly different for either AdV-4 or AdV-7 vaccine components. There were no subjects that demonstrated waning neutralization antibody (NAb) titers against AdV-4 and less than 5% of subjects against AdV-7. Interestingly, there were subjects that had a four-fold increase in NAb titers against either AdV-4 or AdV-7, at various time points post vaccination, suggesting either homotypic or heterotypic re-exposure. This investigation provided strong evidence that the live oral AdV-4 and AdV-7 vaccine induced long-term immunity to protect from AdV-4 and AdV-7 infections.

Keywords: acute respiratory disease; human adenovirus; human respiratory illness; immunity; live vaccine; serology.

Figure 1

Individual neutralizing antibody titer against Adenovirus type 4 and type 7 with geometric means at 95% confidence interval according to time. Neutralizing antibody (NAb) titers of subjects given single dose of live oral adenovirus (AdV)-4 and AdV-7 vaccine by years, post-vaccination (N = 36 for AdV-4 and 41 for AdV-7), 50% NAb titer (NT50) was determined by colorimetric cytopathic effect based neutralization assay against AdV-4 for seronegative (A) and seropositive subjects (B) and against AdV-7 for seronegative (C) and seropositive (D) subjects. NT50 equal to or greater than 4 demonstrates seroconversion and a positive. Statistical significance is indicated as follows: ns, not significant (p value = 0.12), *, p = 0.033; **, p = 0.002; ***, p < 0.001.