Alex Moir ’23
Staphylococcus aureus (S. aureus) is a bacterium often found in both skin and the upper respiratory tract. Despite its native status in the human body, S. aureus can also act as an opportunistic pathogen in immunocompromised hosts. Efforts to create an effective S. aureus vaccine have so far proven unsuccessful due to the diverse array of immunoevasive strategies S. aureus employs. Specifically, Staphylococcal protein A (SpA), a protein expressed on the surface of S. aureus, binds to circulating antibodies and disables their ability to signal other immune cells to kill S. aureus. SpA can also fool immune B cells into secreting nonspecific antibodies for S. aureus. Past attempts at a vaccine-usable SpA were unable to both elicit production of SpA-targeting antibodies and not fool B cells without binding to unwanted immune cell receptors and causing anaphylactic shock or death. To develop this detoxified SpA variant, Stony Brook researcher Dr. Hwan Kim and his team designed and tested 67 new SpA variants.
The team used computer modeling to identify specific regions of SpA where an amino acid change could potentially alter its behavior to meet the design criteria. 67 new candidate variants of SpA were identified and synthesized using recombinant protein production techniques. These candidate SpA variants were then exposed to SpA antibodies isolated from human patient blood samples and binding levels were measured. The variants that still showed binding specificity by SpA antibodies were then screened for inhibitory activity towards B cell receptors. A loss of interaction between a region of the B cell receptors known as Fcγ with SpA variants indicated that the variant would not fool the B cell. The variants that lacked inhibitory activity were then exposed to blood immune cell cultures such as mast cells and basophils to test for inflammatory responses, quantified here as histamine levels in the sample. Ultimately, the researchers identified 2 SpA variants, SpAKKE and SpAKKT, that did not elicit an immune response and therefore are potential vaccine candidates.
The team’s findings provide a promising potential route for preventative care against S. aureus infection. Due to its widespread prevalence, S. aureus infection is common, and exposure to antibiotics used to treat unrelated infections has led to the rapid emergence of antibiotic-resistant S. aureus strains. This rise in antibiotic resistance presents a dire need for preventative measures against S. aureus infection, for which this team’s findings set the groundwork.
 M. Shi, et al., A protein A based Staphylococcus aureus vaccine with improved safety. Vaccine 39, 1-9 (2021). doi: 10.1016/j.vaccine.2021.05.072.