Safety and immunogenicity testing of a melioidosis subunit vaccine candidate in cynomolgus macaques.

Burkholderia pseudomallei, the etiologic agent of melioidosis, is a Gram-negative bacterial pathogen that causes severe disease in humans and animals. In this study, we evaluated the safety and immunogenicity of our lead melioidosis subunit vaccine candidate in cynomolgus macaques. To accomplish this, the 6-deoxyheptan capsular polysaccharide (CPS) from Burkholderia thailandensis E555 was purified using a phenol-free extraction process and then conjugated to CRM197 to generate CPS-CRM197. Highly purified, His-tagless B. pseudomallei Hcp1 (Hcp1-TL) was also produced. Animals immunized with CPS-CRM197 combined with Hcp1-TL and adjuvanted with Alhydrogel plus CpG DNA (ODN 2006) developed robust CPS-specific IgG and opsonizing antibody responses, alongside strong Hcp1-specific IgG and measurable IFN-γ-secreting T-cell responses. Importantly, the vaccine formulations tested were well tolerated, with no adverse events after three doses. Collectively, these studies establish good manufacturing practices-compatible processes for our vaccine antigens and demonstrate the safety and immunogenicity of the subunit vaccine in non-human primates, supporting continued advancement towards a human clinical trial.