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Liposomal Fc Domain Conjugated to a Cancer Vaccine Enhances Both Humoral and Cellular Immunity.

ABSTRACT: Targeted delivery of antigens to antigen-presenting cells (APCs) by utilizing natural anticarbohydrate antibodies is a promising approach for selective uptake and enhanced antigen presentation. Previously, we reported that in the presence of a natural antibody, anti-rhamnose antibody (anti-Rha), the bacterial sugar rhamnose conjugated with liposomal cancer antigen MUC1-Tn enhances antigen presentation by APCs such as dendritic cells by targeting Fc gamma receptors. The idea was to utilize the natural human anti-Rha antibodies present in human serum for targeted delivery of cancer-specific antigens. Recently, we found that the IgG3 antibody isotype was the most prevalent anti-Rha antibody generated in mice immunized with rhamnose-Ficoll (Rha-Ficoll) antigen. In this manuscript, we have conjugated the murine IgG3-Fc with a MUC1-containing cancer vaccine and compared the humoral and cellular immune response to this vaccine with one targeted via the human anti-Rha antibody and to the MUC1 vaccine alone. This Fc approach enhanced antibody production and T-cell proliferation almost to the same level as using the anti-Rha antibody. These results suggest that targeting Fc directly to dendritic cells can be an alternative approach to human anti-Rha for generating effective antigen-primed T-cells.

SUBMITTER: Hossain MK

PROVIDER: S-EPMC6441943 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Liposomal Fc Domain Conjugated to a Cancer Vaccine Enhances Both Humoral and Cellular Immunity.

Hossain Md Kamal MK Vartak Abhishek A Sucheck Steven J SJ Wall Katherine A KA

ACS omega 20190313 3

Targeted delivery of antigens to antigen-presenting cells (APCs) by utilizing natural anticarbohydrate antibodies is a promising approach for selective uptake and enhanced antigen presentation. Previously, we reported that in the presence of a natural antibody, anti-rhamnose antibody (anti-Rha), the bacterial sugar rhamnose conjugated with liposomal cancer antigen MUC1-Tn enhances antigen presentation by APCs such as dendritic cells by targeting Fc gamma receptors. The idea was to utilize the na ...[more]

PMID: 30949616

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Project description:Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella (MMR) vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction for FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans.

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Liposomal Fc Domain Conjugated to a Cancer Vaccine Enhances Both Humoral and Cellular Immunity.

Publications

Liposomal Fc Domain Conjugated to a Cancer Vaccine Enhances Both Humoral and Cellular Immunity.

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