Boosting Immune Response to Hepatitis B DNA Vaccine by Coadministration of Prothymosin α-Expressing Plasmid

Abstract

DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. In this study, we report that coadministration of a hepatitis B virus (HBV) DNA vaccine with prothymosin ␣ as an adjuvant improves antibody responses to HBV S antigen. We also observed higher seroconversion rates and higher antibody titers. Prothymosin ␣ appears to increase the number and affinity of hepatitis B surface antigen-specific, gamma interferon-secreting T cells and to enhance cellular immune response to the PreS2S DNA vaccine. Interestingly, administering the DNA separately from the prothymosin ␣ plasmid abrogated the enhancement of DNA vaccine potency. The results suggest that prothymosin ␣ may be a promising adjuvant for DNA vaccines.Immunization with naked DNA can be defined as the in vivo delivery of an antigen-encoding expression vector into a given tissue for the purpose of the induction of immune responses. This novel immunization approach results in de novo production of correctly folded and glycosylated protein antigens and in certain respects mimics the actions of live attenuated or recombinant virus vaccines. As a consequence, this mode of immunization may mimic natural infection and induce protective immune responses. In animal models, such genetic immunization induces both humoral and cellular immune responses against a range of viral pathogens, such as hepatitis B virus (31), influenza A virus (37, 43), herpes simplex virus (5, 27, 28), rabies virus (48), and human immunodeficiency virus type 1 (6, 45). In spite of the existence of safe and efficacious vaccines, hepatitis B virus (HBV) infection is one of the most common infectious diseases, with an estimated 350 million chronic HBV carriers worldwide (12,22). Patients with chronic hepatitis B are at high risk of developing liver cirrhosis, which is associated with a high rate of mortality due to the development of hepatocellular carcinoma or noncarcinomatous complications of cirrhosis (portal hypertension and liver failure) (19). In addition, these chronically HBV-infected carriers represent a reservoir of HBV. Prophylactic immunization against HBV infections can be achieved with recombinant subunit HBV vaccines (10, 30, 44); however, a small number of individuals do not develop protective immunity even after more than the recommended three hepatitis B surface antigen (HBsAg) inoculations. The incidence of nonresponse in immunocompetent young adults is around 5% but increases up to 30% with age of vaccination or even more in immunocompromised individuals (32). Other problems arising from the use of current HBV vaccines are escape variants with mutations within HBsAg and the requirement of at least three injections to achieve protection. For control of HBV infections and liver disease, efficacious but inexpensive DNA vaccines may thus be promising tools (18). Recent reports have demonstrated the efficacy of DNA-based HBV vaccines. Immunization ...

Duck Enteritis Virus Glycoprotein D and B DNA Vaccines Induce Immune Responses and Immunoprotection in Pekin Ducks

“…Previous studies have shown that intramuscular injection with 200 µg plasmid induces the highest titers of antibodies, and stronger cellular immune responses while vaccination with live attenuated vaccine predominantly induced humoral immune responses [36] . In addition, intramuscularly repeated vaccination with DNA vaccines at a 2-week interval induced potent cellular and humoral responses in animals [37] , [38] . We used the same protocol to achieve a similar level of T cell and humoral responses to DEV in Pekin ducks.…”

Prothymosin Alpha and Immune Responses

“…Similarly, release of proTα upon infection of guinea pigs with an attenuated strain of Pichinde virus led to induction of potent antiviral immunity and consequent viral clearance (Bowick et al, 2010). In terms of in vivo applications, proTα has been used as a potent adjuvant for hepatitis B virus DNA vaccines, where it successfully enhanced both humoral and cellular immune responses (Jin et al, 2005). Impressively, a most recent report showed that proTα displays antiviral activity in other classes than mammals, specifically in fish (tongue sole) infected with megalocytivirus (Zhang & Sun, 2015).…”

In Vivo Sampling of Extracellular β‐Thymosin by Ultrafiltration Probes

“…Extracellular HSPs have been known for their strong adjuvant effect on the associated peptide, 17,18 Thymosin‐α 1, an immunomodulating agent able to enhance the Th1 immune response. It has been reported that coadministration of a hepatitis B virus (HBV) DNA vaccine with prothymosin α as an adjuvant improves antibody responses to HBV S antigen, suggesting prothymosin α may be a promising adjuvant for DNA vaccines 22 . In addition, it has shown that synthetic thymosin α1 exhibits an immunostimulatory action, enhancing specific immunity when injected at different periods of the vaccinal process against Y. pestis virulent strain 231 23 .…”

“…It has been reported that coadministration of a hepatitis B virus (HBV) DNA vaccine with prothymosin ␣ as an adjuvant improves antibody responses to HBV S antigen, suggesting prothymosin ␣ may be a promising adjuvant for DNA vaccines. 22 In addition, it has shown that synthetic thymosin ␣1 exhibits an immunostimulatory action, enhancing specific immunity when injected at different periods of the vaccinal process against Y. pestis virulent strain 231. 23 Using an in vivo ultrafiltration sampling technique (read next paragraph), we are able to detect the extracellular ␤-thymosins in the subcutaneous space of mouse skin.…”