Abstract
BackgroundPre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China.Methodology/Principal FindingsA new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, cross-sectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30–55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significant difference observed for titer or prevalence by gender, age range and geographic origin.ConclusionA simplified, sensitive, standardized, reproducible, and high-throughput assay was developed for the quantitation of NAbs against different Vaccinia strains. The current study provides useful insights for the future development of VTT-based vaccination in Beijing and Anhui provinces of China.
Highlights
Vaccinia Tian Tan virus (VTT) was historically used for the vaccination of millions of Chinese people during the worldwide smallpox prevention campaign, and such programs led to the eradication of Variola in China prior to 1980 [1,2,3,4]
VTT has been used as a virus vector for the development of potential vaccines for Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Human papillomavirus (HPV), Influenza virus subtype H5N1, Aichi virus (AIV), Severe acute respiratory syndrome coronavirus (SARS-CoV), and Rabies virus that can confer protection to immunized animals [5,6,7,8,9,10,11]
Current views on Vaccinia virus (VACV) suggest that it’s immunity is high or existent in the current population born before the early 1980s [12], which may influence both the titer and duration of the antibody response induced by a second distinct Vaccinia recombinant vaccine [13]
Summary
Vaccinia Tian Tan virus (VTT) was historically used for the vaccination of millions of Chinese people during the worldwide smallpox prevention campaign, and such programs led to the eradication of Variola in China prior to 1980 [1,2,3,4]. VTT has been used as a virus vector for the development of potential vaccines for Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Human papillomavirus (HPV), Influenza virus subtype H5N1, Aichi virus (AIV), Severe acute respiratory syndrome coronavirus (SARS-CoV), and Rabies virus that can confer protection to immunized animals [5,6,7,8,9,10,11]. These approaches have been successful in animal models, significant problems remain for the use of VTT vector in humans.
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