Immunogenicity of RSV F DNA Vaccine in BALB/c Mice.

Erdal Eroglu,Swapnil Bawage,Ankur Singh,Vida A Dennis,Shreekumar R Pillai,Shree R Singh,Pooja M Tiwari,Komal Vig

doi:10.1155/2016/7971847

Abstract

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections.

Highlights

Respiratory syncytial virus (RSV), a member of genus Pneumovirus and classified in the family Paramyxoviridae, is the most common cause of severe disease of the lower respiratory tract in infants and the elderly especially in developing countries [1, 2]
The Th1 type immune response is desired for protection against natural RSV infections
All models challenged with wt RSV following the immunization with formalin inactivated RSV (FI-RSV) stimulated the Th2 type allergic response [23,24,25, 29,30,31,32]

Summary

Introduction

Respiratory syncytial virus (RSV), a member of genus Pneumovirus and classified in the family Paramyxoviridae, is the most common cause of severe disease of the lower respiratory tract in infants and the elderly especially in developing countries [1, 2]. Some researchers have been attempting to develop prophylactic antibody therapies targeting RSV F protein [7, 8]. Antiviral drugs such as ribavirin (a nucleoside analog), which targets hepatitis C and other viruses including RSV, ALS-8176 (a new nucleoside analog), and GS5806 (pyrazolo[1,5-a]pyrimidine based RSV fusion inhibitor), and neutralizing monoclonal antibodies such as Palivizumab (Synagis6) and Motavizumab (Numax), are administered to infants at high risk of developing respiratory diseases [9,10,11,12]. As an alternative to expensive therapies, a vaccine conferring long lasting immunity is a less expensive and more efficient option against recurrent RSV infections [10]. The incomplete immunity in response to natural RSV infections is responsible

Methods

Results

Conclusion