A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and Enhanced Protective Immune Response.

Yao Ma,Nan Jiang,Xiu-Juan Zhang,Larry Anderson,Yun-Zhou Yu,Yan-Peng Zheng,Ying Hua,Yuan-Hui Fu,Jin-Sheng He,Xiang-Lei Peng,Yue-Ying Jiao

doi:10.3390/v10010038

Yao Ma, Nan Jiang + Show 9 more

Open Access

https://doi.org/10.3390/v10010038

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Abstract

Human respiratory syncytial virus (RSV) is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F) glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified vaccines, especially with the higher 20 copies, resulted in an enhanced shift toward a Th1-biased antibody and T-cell response, a decrease in pulmonary pathology and virus replication, and a decrease in weight loss after RSV challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of improving the efficacy of DNA vaccine against RSV infection.

Highlights

Human respiratory syncytial virus (RSV) is an enveloped, non-segmented, negative-sense, single-stranded RNA virus in the Pneumoviridae family
We evaluated the ability of built-in CpG-C motif to enhance the immunogenicity of an RSV F protein DNA vaccine
We looked at five or 20 copies of the CpG-C motif cloned into the plasmid encoding RSV F, designated pVAX1-F-CpG5 or pVAX1-F-CpG20, for their ability to enhance the antibody response and direct a Th1 predominant immune response

Summary

Introduction

Human respiratory syncytial virus (RSV) is an enveloped, non-segmented, negative-sense, single-stranded RNA virus in the Pneumoviridae family. It causes respiratory disease throughout life with greatest disease burden in infants and the elderly [1,2]. Despite RSV being discovered over 60 years ago, an effective vaccine is still unavailable [4,5,6]. The first vaccine, a formalin-inactivated, alum adjuvanted RSV (FI-RSV), was evaluated in infants and young children in the 1960s. This vaccine caused enhanced respiratory disease (ERD)

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