The Final Stage of Developing Genetically Modified Inactivated Sabin Vaccine for the Eradication of Poliovirus

Special Article – Medical Microbiology

Austin J Microbiol. 2015; 1(2): 1009.

The Final Stage of Developing Genetically Modified Inactivated Sabin Vaccine for the Eradication of Poliovirus

Pinn Tsin Isabel Yee and Chit Laa Poh*

Virology Research Group, Vice Chancellor’s Office, Sunway University, Bandar Sunway, Kuala Lumpur, Selangor 47500, Malaysia

*Corresponding author: Chit Laa Poh, Virology Research Group, Vice Chancellor’s Office, Sunway University, Bandar Sunway, Kuala Lumpur, Selangor 47500, Malaysia

Received: November 05, 2015; Accepted: December 22, 2015; Published: December 24, 2015

Abstract

The polio vaccine is one of the most successful vaccines which have reduced worldwide poliomyelitis caused by poliovirus infection. The poliovirus is a human enterovirus which belongs to the Picornaviridae family. Formalin- Inactivated Poliovirus Vaccine (IPV) developed by Salk was the first poliovirus vaccine to be licensed in 1955. The IPV was the only poliovirus vaccine available until licensure of the Oral Poliovirus Vaccine (OPV) in1963. The OPV is a live attenuated vaccine that has long-lasting immune response but requires several boosters, is safe and effective. Elimination of poliomyelitis in the developing world was achieved mainly through mass vaccination with the OPV despite its ability to revert to the wild type. However, polio still persistently remained endemic in Afghanistan and Pakistan. One of the most anticipated next generation vaccines is an IPV based on the attenuated Sabin poliovirus strains. An attenuated Sabin IPV (sIPV) has been used in Japan for the past 3 years in their routine immunization program and licensed in China to be introduced in routine immunization in several provinces. The sIPV is produced from poliovirus strains that have an antigenic structure identical to the currently used wild-type strains but were rendered non-pathogenic by genetic manipulations. Of interest would be the manipulations of the IRES within the 5’-NTR to produce geneticallystable OPV strains such as the removal of U-G base-pairs in domain V of the 5’-NTR in the Poliovirus (PV) and insertion of the Cis-acting replication element (cre) from the P2 region to a position near the 5’ end to reduce the risk of loss of this part of the genome through recombination. Other methods include creation of PV strains with high polymerase fidelity, codon pair bias deoptimization and microRNA sequence insertion. Thermostable PV Virus-Like Particles (VLPs) that have similar antigenicity as the wild type PV but are stable enough to allow vaccine production are currently being constructed. The development of such new sIPVs could serve as more promising vaccines to eradicate poliomyelitis from the world.

Keywords: Poliovirus; Poliomyelitis; Vaccine; Genome; sIPV

Introduction

Polio virus vaccines

Inactivated polio vaccine: Poliovirus (PV) is the etiological agent of poliomyelitis and belongs to Enterovirus species C within the Picornaviridae family. Poliomyelitis was a public health scare in the 1950s, even in countries with the best health systems and hygiene practices in place. This thereby led to the raising of funds to support research in the development of a polio vaccine. The Inactivated Poliovirus Vaccine (IPV) was the first poliovirus vaccine to be licensed in 1955. IPV was developed by Salk et al. (1954) and was prepared by formalin-inactivation of three wild-type virulent strains which are the Mahoney (type 1), MEF-1 (type 2) and Saukett (type 3). The United States started using the IPV and it showed such high efficacy that other countries around the world started to follow suit.

Although IPV is considered safe, there is a risk of exposure to the wild type strain during the manufacturing process. Figure 1.1 shows the manufacturing process for the IPV. During monovalent bulk preparation, Vero cells were expanded using two pre-culture steps and cell culture followed by virus culture. The PV was purified using normal flow filtration for clarification, tangential flow filtration for concentration and followed by two chromatography steps involving size exclusion and ion exchange chromatography. Purified virus was inactivated using formaldehyde. Subsequently the IPVs were mixed to obtain trivalent bulk prior to formulation and filling [1]. Due to the need to cultivate large amounts of the live poliovirus which involved complex manufacturing and purification processes, exposure of workers to the live virus must be safely guarded. At the Cutter Laboratories, insufficient inactivation of the IPV led to paralysis in almost 200 vacinees and their contacts [2]. This incident resulted in the temporary halt of the use of IPV and encouraged research groups worldwide to produce a live attenuated polio vaccine. Although IPV has an excellent track record on efficacy, it had poor induction of intestinal immunity, required cold-chain, booster injections and had expensive and potentially dangerous manufacturing processes with the wild type virulent virus. As such, large-scale clinical trials were evaluated using several live attenuated PV strains [3].