Intranasal Coronavirus SARS-CoV-2 Immunization with Lipid Adjuvants Provides Systemic and Mucosal Immune Response against SARS-CoV-2 S1 Spike and Nucleocapsid Protein

Abstract

In this preclinical two-dose mucosal immunization study, using a combination of S1 spike and nucleocapsid proteins with cationic (N3)/or anionic (L3) lipids were investigated using an intranasal delivery route. The study showed that nasal administration of low amounts of antigens/adjuvants induced a primary and secondary immune response in systemic IgG, mIL-5, and IFN-gamma secreting T lymphocytes, as well as humoral IgA in nasal and intestinal mucosal compartments. It is believed that recipients will benefit from receiving a combination of viral antigens in promoting a border immune response against present and evolving contagious viruses. Lipid adjuvants demonstrated an enhanced response in the vaccine effect. This was seen in the significant immunogenicity effect when using the cationic lipid N3. Unlike L3, which showed a recognizable effect when administrated at a slightly higher concentration. Moreover, the findings of the study proved the efficiency of an intranasally mucosal immunization strategy, which can be less painful and more effective in enhancing the respiratory tract immunity against respiratory infectious diseases.

Sex-specific switching of responsive immune pathways in vaccinated diabetic murine model exposed to influenza infection

“…Human seasonal in uenza vaccine Vaxgrip was provided subcutaneously to the four groups (FD-, FD+, MD-, MD+) along with human endogenous lipid emulsion adjuvant derivative of the N3 (cationic) lipid formulations obtained from Merck (Darmstadt, Germany). This adjuvant has been used in our previous studies as well 40,41 and is well established for boosting immunity. Diabetes was induced by streptozotocin (STZ) in two groups (FD + and MD+) and the in uenza viral challenge was provided in all four groups.…”

“…ELISA was performed on the serum separated from the blood samples (0.5 ml) that were collected from all the animal groups in Table 1 on the day of sacri ce following the standard procedure as described before 41 and described in the Supplementary Methods section. Brie y, recombinant H1N1 or H3N2 Hemagglutinin (HA) antigen was used to coat the ELISA plates followed by serum sample incubation, washing, and HRP-labelled conjugate goat-anti-mouse IgG (BioRad, Richmond, CA) antibody incubation.…”

Anionic and Cationic Lipid Adjuvants individually induce distinct adaptive Th1/Th2-type immunity in enhancing post-intranasal immunization response against influenza

“…The vaccine formula was prepared with HA and the N3 emulsion at 1:1 (v/v) to make a nal concentration of 2% N3 lipid formulation. The same adjuvant formulations of L3 and N3 are also used and characterized in our recently published study in SARS-CoV-2 vaccination [27] and also in the previous in uenza [19] and HIV [23], [26] vaccination studies from our lab.…”

Characterization of splenic and systemic immunity by differentially charged lipid adjuvants in enhancing post-intranasal immunization response against influenza

“…The properties of these adjuvants (anionic L3 and cationic N3) have been reported in previously published studies [19][20][21][22][23][24][25][26][27] and also discussed brie y here in the methods section. Previous studies from our and other labs with the anionic L3 adjuvant proved its potential and safety in pre-clinical settings in intranasal administration for in uenza vaccination [19][20][21][22] .…”

“…L3 adjuvant administration in in uenza vaccination reduced the viral load in the lungs, induce higher anti-viral antibody titers in mice and ferrets 21 , and enhanced neutralization potential cell-mediated immunity 19 . The cationic version of the same adjuvant (N3) has been rst used by our lab in 2006 for HIV vaccination 26 and later also studied in in uenza 19 and SARS-CoV-2 vaccination 27 .…”