Staphylococcus aureus toxin antibodies: Good companions of antibiotics and vaccines

Figures & data

Table 1. Key characteristics of vaccines and antibody-based biologics currently in Phase II clinical testing (no active programs are currently in Phase III).

Sponsor	Product type & name	Target antigen(s)	Product composition	Expected mechanism of action	Clinical phase, target population & key endpoints (see www.clinicaltrials.gov)
Pfizer	Vaccine	All surface antigens: Capsular Polysaccharides type 5 & 8 (CP5 & CP8)	2 polysaccharide conjugates (CP5-CRM & CP8-CRM) + 2 recombinant proteins (ClfA & MntC)	Induction of antibodies able to induce opsonophagocytosis and inhibit adhesive properties of the bacterium	Phase IIb in elective spinal
	SA4Ag ( S. aureus 4-Antigen vaccine)
					fusion surgery patients for the prevention of S. aureus blood stream infections and/or deep incisional or organ/space surgical site infections
		Clamping factor A (ClfA)
		Manganese transporter C	Formulation: non-adjuvanted
Novadigm	Vaccine	Surface antigen from Candida albicans: agglutinin-like sequence 3 (Als3)	1 recombinant protein	Induction of protective T-cell response	Phase IIa in patients with STAT3-mutated hyper-IgE syndrome to evaluate immunogenicity of NDV-3A vaccine
	NDV 3A
			Formulation: non-adjuvanted
Xbiotech	Human mAb	Surface protein	1 human mAb against SpA	Induction of antibodies able to block SpA-mediated immune evasion and induce opsonophagocytosis	Phase I-II in hospitalized patients with bacteremia due to S. aureus to evaluate efficacy (sterile blood culture) from date of randomization of 514G3 antibody in addition to standard of care antibiotic treatment
	514G3	Staphylococcal protein A (SpA)
MedImmune	Human mAb	Toxin	1 human mAb against Hla	Neutralization of toxicity associated with Hla	Phase II in mechanically ventilated patients to evaluate efficacy of MEDI4893 as measured by clinical symptoms of pneumonia and other S. aureus serious infection
		α-hemolysin (Hla)
	MEDI4893
Arsanis	Human	Toxins	2 human mAbs:	Neutralization of toxicity associated with Hla and leukocidins	Phase II in in Heavily Colonized, Mechanically Ventilated Subjects to evaluate efficacy of ASN100 as measured by clinical symptoms of pneumonia and other S. aureus serious infection
	mAb combination of ASN-1 and ASN-2	α-hemolysin (Hla)
			1) ASN-1 against Hla and with cross-reactivity to four of the five leukocidins, HlgAB, HlgCB, LukED, and LukSF
			2) ASN-2 neutralizes the fifth leukocidin LukAB
	ASN100
Aridis	Human mAb	Toxin	1 human mAb against Hla	Neutralization of toxicity associated with Hla	Phase I-II in patients who have severe pneumonia caused by S. aureus to evaluate efficacy (survival, bacterial load from respiratory samples) of AR-301 in addition to standard of care antibiotic treatment
		α-hemolysin (Hla)
	AR-301

Figure 1. Expected mechanism of action of anti-toxin antibody-based biologics in conjunction with antibiotic therapy. Antibiotic prophylaxis may prevent a S. aureus infection (blue spheres). Once an infection is established toxins accumulate in the tissues. Antibiotic therapy alone may not be able to effectively block disease progression mediated by accumulated toxins even if it is able to reduce bacterial counts. A combined anti-toxin/antibiotic therapy may be able to both reduce CFUs and neutralize toxin activity blocking disease progression. This mechanism may be particularly relevant in diseases such as S. aureus pneumonia in which toxins play a key role and disease reaches its acute phase quickly.