Development of a ferritin-based nanoparticle vaccine against the SARS-CoV-2 Omicron variant

A new SARS-CoV-2 variant named Omicron (B.1.1.529) discovered initially in South Africa has recently been proposed as a variant of concern (VOC) by the World Health Organization, because of its high transmissibility and resistance to current vaccines and therapeutic antibodies. Therefore, rapid development of vaccines against prevalent variants including Omicron is urgently needed for COVID-19 prevention. Here, we designed a self-assembling ferritin-based nanoparticle (FNP) vaccine against the SARS-CoV-2 Omicron variant. The purified Fc-RBDOmicron automatically formed a dimer depending on the nature of the Fc tag, thus assembling onto the nanoparticles by the Fc-protein A tag interaction (FNP-Fc-RBDOmicron). The results of hACE2-transgenic mice immunization showed that SARS-CoV-2 Omicron RBD-specific IgG titer induced by FNP-Fc-RBDOmicron was much higher than that by Fc-RBDOmicron. Consistently, the sera showed a higher neutralizing activity against SARS-CoV-2 Omicron BA.1 and BA.2 in the FNP-Fc-RBDOmicron immunized mice, indicating that immunization of a self-assembling ferritin-based nanoparticle vaccine offers a robust humoral immune response against Omicron variants. This study offers a great potential for the quick response of the emerging SARS-CoV-2 variants and affords versatility to develop universal vaccines against other emerging and reemerging coronaviruses in the future.

Construction, expression and characterization of a dual cancer-specific fusion protein targeting carcinoembryonic antigen in intestinal carcinomas.

The abundantly expressed carcinoembryonic antigen (CEA) on several cancer types is an attractive target for antibody-directed therapy. However, CEA is also present in some normal tissues. Here, we produced a dual functioning protein, designated as CAtin that exhibits both specific binding and killing functions, by fusing a tumor-specific apoptosis-inducing molecular Apoptin to C-terminus of an anti-CEA single-chain disulfide-stabilized Fv antibody (scdsFv). The CAtin proteins were expressed in Escherichia coli (E. coli), refolded and purified on an immobilized Ni2+ affinity chromatography column. SDS-PAGE and Western blotting revealed that the recombinant protein was well-expressed and the yield was approximately 250mg/L. We demonstrated by flow cytometry and immunofluorescence assays that CAtin could bind specifically to human colon carcinoma cells (LoVo), but almost not to human uterine cervix (Hela). The results suggest that CAtin is active and specific toward CEA-positive cells and may potentially be used in CEA-targeted cancer therapy.

Prediction of the Th/B cell epitopes on HA of influenza virus(H1N1)and antigenicity analysis / 中国免疫学杂志

Objective:To predict Th/B cell epitopes in HA of influenza virus(H1N1)and analyze antigenicity of the candidate epitopes in order to develop epitope-bacterin by the way of bioinformatics.Methods:The HA amino acid sequences of infiuenza virus(H1N1),which the viral infection was prevalent recently,were downloaded from Genbank.The Th/B cell epitopes were predicted and analyzed by bioinformatics methods.Then,specificity and conservation of the candidate epitopes were estimated.Finally,antigenicity of the candidate epitopes was identified by influenza virus(H1N1)positiVe serum samples of mice.Results:Three Th/B cell epitopes containing HA_(73-87),HA_(125-139),HA_(188-205) were acquired Two of the candidate epitopes were in a relatively conserved domain of HA1,and a deal of 2006-2009 influenza virus(H1N1)isolates contained the sequences.Moreover,the candidate epitopes were showedin a distinct antibody combining reactivity with the influenza virus (H1N1)positive serum of mice,which inferred the predicted epitopes to be functional ones.Conclusion:The selected epitopes are able to be functional HA Th/B cell epitopes of influenza virus(H1N1).Our study also establish the foundations for the further research of influenza virus infectlon and immunity mechanism,the recognition of influenza virus(H1N1)functional epitope and the development of epitope vaccines.

Prediction of the Th/B cell epitopes on HA of influenza virus(H1N1) and antigenicity analysis / 中国免疫学杂志

Objective:To predict Th/B cell epitopes in HA of influenza virus(H1N1) and analyze antigenicity of the candidate epitopes in order to develop epitope-bacterin by the way of bioinformatics.Methods:The HA amino acid sequences of influenza virus (H1N1),which the viral infection was prevalent recently,were downloaded from Genbank.The Th/B cell epitopes were predicted and analyzed by bioinformatics methods.Then,specificity and conservation of the candidate epitopes were estimated.Finally,antigenicity of the candidate epitopes was identified by influenza virus (H1N1) positive serum samples of mice.Results:Three Th/B cell epitopes containing HA73-87,HA125-139,HA188-205 were acquired.Two of the candidate epitopes were in a relatively conserved domain of HA1,and a deal of 2006-2009 influenza virus (H1N1) isolates contained the sequences.Moreover,the candidate epitopes were showedin a distinct antibody combining reactivity with the influenza virus (H1N1) positive serum of mice,which inferred the predicted epitopes to be functional ones.Conclusion:The selected epitopes are able to be functional HA Th/B cell epitopes of influenza virus (H1N1).Our study also establish the foundations for the further research of influenza virus infection and immunity mechanism,the recognition of influenza virus (H1N1) functional epitope and the development of epitope vaccines.