The Group A Streptococcal Vaccine Candidate VAX-A1 Protects against Group B <i>Streptococcus</i> Infection via Cross-Reactive IgG Targeting Virulence Factor C5a Peptidase
Sinead McCabe,
Elisabet Bjånes,
Astrid Hendriks,
Zhen Wang,
Nina M. van Sorge,
Lucy Pill-Pepe,
Leslie Bautista,
Ellen Chu,
Jeroen D. C. Codée,
Jeff Fairman,
Neeraj Kapoor,
Satoshi Uchiyama,
Victor Nizet
Affiliations
Sinead McCabe
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
Elisabet Bjånes
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
Astrid Hendriks
Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Zhen Wang
Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands
Nina M. van Sorge
Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Lucy Pill-Pepe
Vaxcyte, Inc., San Carlos, CA 94070, USA
Leslie Bautista
Vaxcyte, Inc., San Carlos, CA 94070, USA
Ellen Chu
Vaxcyte, Inc., San Carlos, CA 94070, USA
Jeroen D. C. Codée
Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands
Jeff Fairman
Vaxcyte, Inc., San Carlos, CA 94070, USA
Neeraj Kapoor
Vaxcyte, Inc., San Carlos, CA 94070, USA
Satoshi Uchiyama
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
Victor Nizet
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
Group B Streptococcus (Streptococcus agalactiae or GBS) is the leading infectious cause of neonatal mortality, causing roughly 150,000 infant deaths and stillbirths annually across the globe. Approximately 20% of pregnant women are asymptomatically colonized by GBS, which is a major risk factor for severe fetal and neonatal infections as well as preterm birth, low birth weight, and neurodevelopmental abnormalities. Current clinical interventions for GBS infection are limited to antibiotics, and no vaccine is available. We previously described VAX-A1 as a highly effective conjugate vaccine against group A Streptococcus that is formulated with three antigens, SpyAD, streptolysin O, and C5a peptidase (ScpA). ScpA is a surface-expressed, well-characterized GAS virulence factor that shares nearly identical sequences with the lesser studied GBS homolog ScpB. Here, we show that GBS C5a peptidase ScpB cleaves human complement factor C5a and contributes to disease severity in the murine models of pneumonia and sepsis. Furthermore, antibodies elicited by GAS C5a peptidase bind to GBS in an ScpB-dependent manner, and VAX-A1 immunization protects mice against lethal GBS heterologous challenge. These findings support the contribution of ScpB to GBS virulence and underscore the importance of choosing vaccine antigens; a universal GAS vaccine such as VAX-A1 whose formulation includes GAS C5a peptidase may have additional benefits through some measure of cross-protection against GBS infections.
