Abstract
Nanoemulsion adjuvants-based vaccines have potent induced immune responses against methicillin-resistant Staphylococcus aureus (MRSA) infection. However, the efficacies and immune responses of different antigen-attaching ways on self-made nanoemulsion adjuvants remain unknown. In this study, we designed three formulations of nanoemulsion adjuvants (encapsulation, mixture, and combination) to explore their immune response-enhancing effects and their underlying mechanism in a systemic infection model of MRSA. Our results showed that the three nanoemulsion-attachment ways formulated with a fusion antigen of MRSA (HlaH35LIsdB348–465) all improved humoral and cellular immune responses. When compared with the mixture and combination formulations, the nanoemulsion-encapsulation group effectively promoted the antigen uptake of dendritic cells (DCs) in vitro, the activation of DC in draining lymph nodes and the delayed release of antigen at injection sites in vivo. Moreover, the encapsulation group induced a more ideal protective efficacy in a MRSA sepsis model by inducing more potent antibody responses and a Th1/Th17 biased CD4+ T cell response when compared with the other two attachment ways. Our findings suggested that the encapsulated formulation of vaccine with nanoemulsion adjuvant is an effective attachment way to provide protective immunity against MRSA infection.
Highlights
With increasing number of Methicillin-resistant Staphylococcus aureus (MRSA) strains emerging in hospitals, there is an urgent need to develop an effective vaccine to combat MRSA infection.[1]
The scanning electron microscopy (SEM) images show that the encapsulated formulation yielded spherical particles with uniform distribution and the particle surfaces were rough with sags and crests (Fig. 1B)
Recent studies have shown that particles with smaller diameters ranging from 1 to 100 nm can be transported more rapidly and captured more efficiently by the dendritic cells (DCs) than larger particles due to penetrating tissue barriers and quick transport to the draining lymph nodes.[34]
Summary
With increasing number of Methicillin-resistant Staphylococcus aureus (MRSA) strains emerging in hospitals, there is an urgent need to develop an effective vaccine to combat MRSA infection.[1] As an ingredient of vaccines, adjuvants are indispensable for enhancing and directly inducing robust and extensive adaptive immune responses associated with vaccine antigens.[2,3] Currently, many public and private initiatives have designed S. aureus vaccines containing adjuvants (such as aluminium salts and emulsion adjuvants) that are in pre-clinical or clinical trials.[4] Aluminum salts are widely used as vaccine adjuvants due to their potential to increase antigen immunogenicity.[5,6,7,8] Emulsion adjuvants (such as AS03 by GlaxoSmithKline and MF59 by Novartis) have been approved in the USA and the European Union.[9] Recently, NB-001, a novel emulsion adjuvant, Nanotechnology is widely used in vaccine development for its ability to improve the immunogenicity of antigens.[15] Several nanovaccine delivery systems (such as nanoemulsions and nanoparticles) have shown signi cant potential for improving immune responses.[16] In particular, nanoemulsions-based vaccines have displayed robust protective efficacy in bacterial vaccine development.[13,14] Our recent study has indicated that a nanoemulsion-based adjuvant potently induces strong immune responses and can effectively improve the stability of bovine serum albumin or recombinant protein HlaH35LIsdB348–465 (derived from the Hla and IsdB genes).[17,18]
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