Immunotherapy Targeting Adenosine Synthase A Decreases Severity of Staphylococcus aureus Infection in Mouse Model

Abstract

Staphylococcus aureus is a severe pathogen found in the community and in hospitals. Most notably, methicillin-resistant S. aureus (MRSA) is resistant to almost all antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments such as immunotherapeutic approaches. Previous research showed that S. aureus exploit the immunomodulatory attributes of adenosine to escape host immunity. In this study, we investigated adenosine synthase A (AdsA), an S. aureus cell wall–anchored enzyme as possible targets for immunotherapy. Mice vaccinated with aluminum hydroxide–formulated recombinant AdsA (rAdsA) induced high-titer anti-AdsA antibodies, thereby providing consistent protection in 3 mouse infection models when challenged with 2 S. aureus strains. The importance of anti-AdsA antibody in protection was demonstrated by passive transfer experiments. Moreover, AdsA-specific antisera promote killing S. aureus by immune cells. Altogether, our data demonstrate that the AdsA is a promising target for vaccines and therapeutics development to alleviate severe S. aureus diseases.

Broad and Effective Protection against Staphylococcus aureus Is Elicited by a Multivalent Vaccine Formulated with Novel Antigens

“…A previous study performed in our laboratory demonstrated that mice vaccinated with recombinant AdsA (rAdsA) induced high titers of anti-AdsA antibodies and provided consistent protection in three mouse infection models under conditions of challenge with S. aureus clinical isolates (19). The remaining two antigens, PmtA and PmtC, belong to Pmt ABC transporter family, an essential S.…”

Clumping factor B is an important virulence factor during Staphylococcus aureus skin infection and a promising vaccine target

“…These have included vaccination with ClfA [12], Als3p [28] and adenosine synthase A [29] in combination with alum and SasX combined with Freund’s adjuvant [30]. These vaccines have had variable efficacy, with only modest protection against SSTIs when ClfA [12] was used as vaccine antigen, supporting the notion that multiple CWA proteins may need to be targeted simultaneously, whereas Als3p [28] and adenosine synthase [29] offered significant protection. In the case of SasX [30], Freund’s adjuvant was used, limiting the potential for translation to humans.…”

Invasive Methicillin-Resistant Staphylococcus aureus USA500 Strains from the U.S. Emerging Infections Program Constitute Three Geographically Distinct Lineages

“…Inflammation may contribute to more frequent transmission and spread of the bacteria by causing rashes and skin damage. The finding that the disrupted adsA gene is common in clinical USA500 MRSA isolates from the United States may also be significant in the future given that the encoded surface protein is a potential vaccine target ( 54 ).…”