Porous PLGA microsphere as a vaccine adjuvant against COVID-19
Poly(lactic-co-glycolic acid)(PLGA)nano-/microspheres have been proven to be effective as vaccine adjuvants.In current studies,the investigations on PLGA vaccine delivery microspheres have mainly focused on improving antigen loading/adsorption efficiency or co-delivery of multiple adjuvants to enhance the immunization effect.However,there is still a lack of discussion on the impact of the structural diversity of microspheres in promoting the vaccination effects.By rationalizing the design of the microsphere structure,we describe that the development of an effective SARS-CoV-2 vaccine adjuvant was achieved by the post-loading of SARS-CoV-2 antigen into porous PLGA microspheres,which provided non-destructive loading and prolonged release of antigen.In this work,PLGA porous microspheres and solid microspheres were prepared with the emulsification method,and there was no significant difference in microsphere particle size and surface potential between the two,except for the porous microspheres having cavities internally and tiny pores on the surface.Such characteristics of"large inner pores and tiny outer pores"enabled the antigen encapsulation efficiency to reach 10.81％at the antigen input concentration of 5.71 mg/mL.In terms of prolonging the in vivo retention of the antigen,the release endpoint in the antigen-loaded porous microspheres was prolonged to 15 days compared with that of the free antigen at 3 days and that of the solid microsphere-mixed antigen at 5 days.Concerning the enhancement of humoral immunization,compared with the solid microsphere vaccine group mixed with SARS-CoV-2 antigen,the porous microsphere vaccine group loaded with SARS-CoV-2 antigen had a higher onset of effect as the maximum value of the IgG titer rising rate,Vmax was 1.73 times higher;and the onset of effect was much earlier,as the time to reach the Vmax was 2.8 days earlier;also,the IgG antibody titer of which was higher during 6～16 weeks post-immunization,presenting a better antibody maintenance effect.
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