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

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.

Covax-19/Spikogen® vaccine based on recombinant spike protein extracellular domain with Advax-CpG55.2 adjuvant provides single dose protection against SARS-CoV-2 infection in hamsters

“…Advax-CpG is a proprietary adjuvant formulation which combines Advax, a non-reactogenic adjuvant based on delta inulin, with a human toll-like receptor 9 (TLR-9) agonist oligonucleotide (CpG55.2) that was developed using artificial intelligence [14] , [15] . Advax-CpG adjuvant has been tested in many preclinical studies [16] , [17] , [18] , [19] and also in human clinical trials, including against Influenza [NCT03945825; NCT03038776] and Hepatitis B [NCT01951677], where it was shown to enhance vaccine immunogenicity while maintaining a satisfactory safety profile. Advax-CpG adjuvant was previously whown to be effective in enhancing coronavirus vaccine protection, as demonstrated in models of severe acute respiratory syndrome (SARS) [20] and Middle East respiratory syndrome (MERS) [21] .…”

Riding the wave of innovation: immunoinformatics in fish disease control

“…However, when utilised alone in vaccine design, epitope vaccines are linked with low protection, which can be overcome by conjugating antigenic epitopes with adjuvants and helper peptides. Several roles for vaccine adjuvants have been proposed; (i) dose-sparing strategy; (ii) accelerating seroconversion rates by enhancing antibody and cell-mediated immune responses; (iii) diversifying the adaptive immune profile and (iv) enhancing vaccine production by using smaller amounts of antigen ( Honda-Okubo, Baldwin & Petrovsky, 2021 ; Lemoine et al, 2021 ). Toll-like receptor (TLR) agonists, antimicrobial peptides and helper peptides are the most common adjuvants used in peptide-based vaccine construction ( Shanmugam et al, 2012 ; Gupta et al, 2020 ).…”

An Advax-CpG55.2™ adjuvanted recombinant spike protein vaccine protects cynomolgus macaques from a homologous SARS-CoV-2 virus challenge

“…CpG55.2 was the first human vaccine adjuvant to be designed by artificial intelligence [14] , [15] . Advax-CpG adjuvant has been shown in preclinical studies to significantly boost vaccine immunogenicity with a positive safety profile [16] , [17] , [18] , [19] . Advax-CpG adjuvant was a key part of previous coronavirus vaccines shown to be protective against severe acute respiratory syndrome coronavirus (SARS-CoV) [20] and Middle East respiratory syndrome coronavirus (MERS-CoV) [21] .…”