Next-generation anti–Staphylococcus aureus vaccines: A potential new therapeutic option for atopic dermatitis?

• Published in: Journal of allergy and clinical immunology Vol. 143; no. 1; pp. 78 - 81
• Main Authors: Clowry, Julianne, Irvine, Alan D., McLoughlin, Rachel M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019; Elsevier Limited
• Subjects: Adjuvants; Aluminum sulfate; Antibiotics; Antimicrobial agents; Atopic dermatitis; Capsular polysaccharides; Colonization; Dermatitis; Eczema; Immunization (passive); Interleukin 13; Interleukin 4; Leukocidin; Lymphocytes; Lymphocytes T; Monoclonal antibodies; Patients; Peptides; Phenols; Proteins; Risk groups; Skin; Staphylococcus aureus; Streptococcus infections; T cell; vaccine; Vaccines; New York; United States > US; China; atopic dermatitis; vaccine; T cell; Staphylococcus aureus
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2018.08.038

Disease severity in patients with atopic dermatitis (AD) is directly correlated with colonization by Staphylococcus aureus.1 An increasing body of evidence now also supports a role for S aureus in the pathogenesis of AD in genetically susceptible subjects.2 Increased prevalence of S aureus preceding and coinciding with AD onset in an infant cohort suggests that early skin colonization can contribute to the development of clinical AD.3 However, these findings only partially explain the complex role of this organism given that another birth cohort4 did not demonstrate S aureus colonization before development of infantile AD but did show a protective effect of commensal staphylococci against later development of AD. Research is currently underway to investigate the effects of dupilumab, an anti–IL-4 receptor α blocker targeting the TH2 cytokines IL-4 and IL-13 in S aureus–colonized versus noncolonized patients with AD.12 However, active infection causing flares still requires the use of antibiotics, highlighting the role of alternative approaches, including active and passive vaccination strategies (Table I).13-23 Passive immunization strategies using mAbs against specific S aureus toxins are under investigation, although typically as adjuncts to standard antibiotic regimens in high-risk patient groups. Reference Active prophylactic vaccines 1 NDV-3: recombinant Candida albicans Als3p adhesion protein (homologous to S aureus surface proteins) with alum adjuvant NovaDigm Therapeutics, Brookline, Mass 1 2 2 NCT01273922 NCT02996448 NCT03455309 Schmidt et al, 201213 Not published Not published 2 S aureus capsular polysaccharides CP5 and CP8 conjugated to TT, mutated detoxified AT and ClfA ± AS03B adjuvant GlaxoSmithKline, Research Triangle Park, NC 1 NCT01160172 Levy et al, 201514 3 STEBVax: recombinant SEB with alum adjuvant Integrated BioTherapeutics, Gaithersburg, Md 1 NCT00974935 Chen et al, 201615 4 HI, SpA5, mSEB, MntC recombinant proteins and aluminum phosphate adjuvants Olymvax, Chengdu, China 1 1 NCT02820883 NCT02804711 Not published Not published 5 SA3Ag/SA4Ag Pfizer, New York, NY SA3Ag: CP5, CP8, conjugated to CRM197 and recombinant ClfA SA4g: CP5, CP8, conjugated to CRM197, recombinant ClfA and MntC 1 1/2 1/2 1 1/2a 2b NCT01018641 NCT01364571 NCT01643941 NCT02364596 NCT02492958 NCT02388165 Nissen et al, 201516 Marshall et al, 201617 Frenck RW Jr, et al, 201718 Creech et al, 201719 Begier et al, 201720 Not published Not published 6 Recombinant α-toxoid (rAT) and subunit of Panton-Valentine leukocidin (rLukS-PV).