Current and next-generation formulation strategies for inactivated polio vaccines to lower costs, increase coverage, and facilitate polio eradication

Abstract

Implementation of inactivated polio vaccines (IPV) containing Sabin strains (sIPV) will further enable global polio eradication efforts by improving vaccine safety during use and containment during manufacturing. Moreover, sIPV-containing vaccines will lower costs and expand production capacity to facilitate more widespread use in low- and middle-income countries (LMICs). This review focuses on the role of vaccine formulation in these efforts including traditional Salk IPV vaccines and new sIPV-containing dosage forms. The physicochemical properties and stability profiles of poliovirus antigens are described. Formulation approaches to lower costs include developing multidose and combination vaccine formats as well as improving storage stability. Formulation strategies for dose-sparing and enhanced mucosal immunity include employing adjuvants (e.g. aluminum-salt and newer adjuvants) and/or novel delivery systems (e.g. ID administration with microneedle patches). The potential for applying these low-cost formulation development strategies to other vaccines to further improve vaccine access and coverage in LMICs is also discussed.

Correlating physicochemical and biological properties to define critical quality attributes of a recombinant AAV vaccine candidate

“…For example, many traditional vaccine antigen platforms (e.g., inactivated viruses and recombinant proteins) can undergo significant loss in their antigenicity values as measured by in vitro potency assays, but in vivo assays are more forgiving and a relatively small loss in immunogenicity is observed. Recent examples of this phenomenon include stressed samples of inactivated polio vaccine 102 and a SARS-CoV-2 RBD vaccine candidate 103 . In this work, however, AC3 samples with increasing exposure to thermal stress correlated with reduced gene expression ( in vitro cell-based assay) and total antibody (mouse immunogenicity assay) levels.…”

“…Recent examples of this phenomenon include stressed samples of inactivated polio vaccine 102 and a SARS-CoV-2 RBD vaccine candidate 103 . In this work, however, AC3 samples with increasing exposure to thermal stress correlated with reduced gene expression (in vitro cell-based assay) and total antibody (mouse immunogenicity assay) levels.…”

Threat of resurgence or hope for global eradication of poliovirus?

“…Recently, a large phase II/III trial demonstrated comparable safety and immunogenicity of a three-dose vaccination series with low-dose sIPV, relative to vaccination with the conventional IPV [52]. Development of multidose, combination, and thermostable IPV formulations would increase accessibility of the IPV vaccine [51 ▪ ].…”

“…However, the prospect of worldwide IPV-exclusive immunization necessitates efforts to make IPV more accessible in all settings. Part of the reason the IPV is far more expensive to manufacture than the OPV is that manufacturing the Salk IPV requires generating high volumes of wildtype poliovirus that must be purified, inactivated, and subjected to biocontainment [50,51 ▪ ]. Significant resources have been directed toward the generation of IPV produced from Sabin strains (sIPV), to lower the cost and biosafety risk associated with traditional IPV vaccination [50,51 ▪ ].…”

“…Part of the reason the IPV is far more expensive to manufacture than the OPV is that manufacturing the Salk IPV requires generating high volumes of wildtype poliovirus that must be purified, inactivated, and subjected to biocontainment [50,51 ▪ ]. Significant resources have been directed toward the generation of IPV produced from Sabin strains (sIPV), to lower the cost and biosafety risk associated with traditional IPV vaccination [50,51 ▪ ]. Recently, a large phase II/III trial demonstrated comparable safety and immunogenicity of a three-dose vaccination series with low-dose sIPV, relative to vaccination with the conventional IPV [52].…”