Advax-CpG Adjuvant Provides Antigen Dose-Sparing and Enhanced Immunogenicity for Inactivated Poliomyelitis Virus Vaccines.

Yoshikazu Honda-Okubo,Nikolai Petrovsky,Jeremy Baldwin

doi:10.3390/pathogens10050500

Yoshikazu Honda-Okubo, Nikolai Petrovsky + Show 1 more

Open Access

https://doi.org/10.3390/pathogens10050500

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Abstract

Global immunization campaigns have resulted in a major decline in the global incidence of polio cases, with wild-type poliovirus remaining endemic in only two countries. Live oral polio vaccine (OPV) played a role in the reduction in polio case numbers; however, the risk of OPV developing into circulating vaccine-derived poliovirus makes it unsuitable for eradication programs. Trivalent inactivated polio virus (TIPV) vaccines which contain formalin-inactivated antigens produced from virulent types 1, 2 and 3 reference polio strains grown in Vero monkey kidney cells have been advocated as a replacement for OPV; however, TIPVs have weak immunogenicity and multiple boosts are required before peak neutralizing titers are reached. This study examined whether the incorporation of the novel polysaccharide adjuvant, Advax-CpG, could boost the immunogenicity of two TIPV vaccines, (i) a commercially available polio vaccine (IPOL®, Sanofi Pasteur) and (ii) a new TIPV formulation developed by Statens Serum Institut (SSI). Mice were immunized intramuscularly based on recommended vaccine dosage schedules and serum antibody titers were followed for 12 months post-immunization. Advax-CpG significantly enhanced the long-term immunogenicity of both TIPV vaccines and had at least a 10-fold antigen dose-sparing effect. An exception was the poor ability of the SSI TIPV to induce serotype type 1 neutralizing antibodies. Immunization with monovalent IPVs suggested that the low type 1 response to TIPV may be due to antigen competition when the type 1 antigen was co-formulated with the type 2 and 3 antigens. This study provides valuable insights into the complexity of the formulation of multivalent polio vaccines and supports the further development of adjuvanted antigen-sparing TIPV vaccines in the fight to eradicate polio.

Highlights

Global immunization campaigns have resulted in a major decline in the global incidence of polio cases, with wild-type poliovirus remaining endemic in only two countries
To mimic the manufacturer’s recommended vaccine schedule in human babies, BALB/c mice were immunized with four doses of IPOL® vaccine at weeks 0, 3, 7 and 12 with IPOL® alone or formulated with Advax or Advax-CpG adjuvant
While ELISAs could be performed on individual mice samples, due to larger sera requirements for the neutralization titer (NT) assays, these were unable to be performed on individual mice, with sera from each member of a group being assembled into a single pooled sample to run the NT assay

Summary

Introduction

Global immunization campaigns have resulted in a major decline in the global incidence of polio cases, with wild-type poliovirus remaining endemic in only two countries. Trivalent inactivated polio virus (TIPV) vaccines which contain formalin-inactivated antigens produced from virulent types 1, 2 and 3 reference polio strains grown in Vero monkey kidney cells have been advocated as a replacement for OPV; TIPVs have weak immunogenicity and multiple boosts are required before peak neutralizing titers are reached. IPV vaccines currently do not contain adjuvant, animal studies have shown the feasibility of using various adjuvants including MF59, calcium, aluminum hydroxide, vitamin D and TLR9active cytosine-phosphodiester-guanosine (CpG)-motif containing oligonucleotides in IPV vaccines [9,10,11,12,13] Most of these studies only evaluated adjuvants with the IPV in their monovalent form and not formulated as TIPV, limiting the interpretation of such results. These studies do support the potential benefit of adjuvants for enhancing

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