TABLE 1.

Some putative vaccine candidates which could be considered in vaccine development against Staphylococcus aureus.

Putative macromolecules	Features	Advantage	Disadvantage	References
Polysaccharide intercellular adhesion (PIA)	Surface polysaccharide poly-N-acetyl-β-(1-6)-glucosamine also known as PIA	Produced in vitro by either S. aureus or Staphylococcus epidermidis with high levels of acetate substituting for amino groups; generate opsonic and protective antibodies PIA has been extensively evaluated as a putative candidate for vaccine development	Immunization with PIA and other polysaccharides must be boosted or conjugated to a safe protein carrier	Maira-Litrán et al., 2005; Maira-Litrán et al., 2012; Miller et al., 2020
Teichoic acid	(A) Glycerol and ribitol phosphate copolymer by phosphodiester bonds (B) It is assigned as main macromolecule to the primary attachments and accumulation phase in biofilm formation (C) It is chiefly important in inflammation and immune evasion	One of the main Gram-positive bacteria-adhesive macromolecules In a study, the efficacy of mAb was determined as >90% against CoNS clinical isolates. Up to 90% of bacterial killing activity was detected at doses <10 μg/ml as an apt opsonophagocytic result, which prevents related infections in animal models	Immunization with PIA and other polysaccharides must be boosted	Ali et al., 2020; van Dalen et al., 2020
Accumulation-associated protein	Presence in both S. aureus and S. epidermidis that plays an essential role in the attachment and aggregation of biofilm phases	Polyclonal antibodies inhibit biofilm formation Its conjugation to a confirmed protective polysaccharide, such as PIA, could eliminate the biofilm formation process by inducing cellular immunity-related immunoglobulin subtypes (IgG2a and IgG2b) to activate memory cells	Arisen antibodies to AaP have no effect on polysaccharide-dependent biofilm-forming S. aureus and S. epidermidis	Yan et al., 2014
Fibronectin binding protein A	Presence in S. aureus	Specific antipeptide immunoglobulin (Ig) G and IgA antibodies were detected in the serum and respiratory mucosa of vaccinated mice. Responses to the major pilus backbone protein Spy0128 showed robust antibody responses to this antigen both systemically and in the respiratory and intestinal mucosa	The mechanism(s) of protection are unclear	Clow et al., 2020
Virulence factor	Secreted factors α-hemolysin, staphylococcal enterotoxin B, and the three surface proteins staphylococcal protein A, iron surface determinant B N2 domain, and manganese transport protein C	Induce comprehensive cellular and humoral immune responses to reduce bacterial loads, inflammatory cytokine expression, and inflammatory cell infiltration and decrease pathology after challenge with a sub-lethal dose of S. aureus	No significant differences in lymphocyte subset distribution and serous cytokine levels (IL-4, IL-5, TNF-α, IFN-γ, IL-2, and IL-6) between the vaccine and the placebo groups	Creech et al., 2020; Zeng et al., 2020; Alabdullah et al., 2021
Phosphatidylinositol phosphodiesterase	Secreted by extracellular pathogens such as S. aureus	Strong humoral response in the vaccine mice that provided 75% protection against S. aureus	Large-scale in vivo studies are called	Soltan et al., 2020

AaP, accumulation-associated protein; TA, teichoic acid; mAB, monoclonal antibody.