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Clostridioides difficile vaccine + CpG oligodeoxynucleotide (PF-07831694) is an investigational bivalent protein subunit vaccine developed by Pfizer for the prevention of primary Clostridioides difficile infection (CDI) in older adults (aged 65 and older) and other at-risk populations. The vaccine is an updated formulation of Pfizer's previous candidate (PF-06425090), containing the same genetically modified and chemically detoxified C. difficile toxoids A and B (TxdA DS and TxdB DS) but formulated with a CpG oligodeoxynucleotide adjuvant (CpG 24555) instead of aluminum hydroxide alone. The CpG adjuvant acts as a Toll-like receptor 9 (TLR9) agonist to enhance the immune response, particularly in older adults who often exhibit immunosenescence. By eliciting robust neutralizing antibody responses against both major pathogenic toxins (TcdA and TcdB), the vaccine aims to prevent the cytotoxic effects that drive CDI symptoms, such as severe diarrhea and colitis. Following promising Phase 2 safety and immunogenicity results, the vaccine has advanced to Phase 3 clinical development in the global BEETHOVEN trial (NCT07282665).
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