Anti-tumor vaccine efficacy depends on adjuvant type and associates with induced IgG subclass and glycosylation profiles.

Abstract

Vaccination with tumor-(neo) antigen plus adjuvant is emerging as a promising cancer-therapy. However, as different adjuvants induce distinct immune cell and antibody (Ab) responses, selecting the right adjuvants remains challenging. Here, we evaluated the following vaccine adjuvants to promote protection against tumor-growth in mice and correlated IgG subclass and Fc N-glycosylation responses: Alum; the toll-like receptor activators Poly(I:C) and MPLA; Alum-Poly(I:C); and the more inflammatory water-in-oil adjuvants Montanide, IFA, CFA, and M.tb.-enriched (e)CFA. While Alum and Montanide failed to protect, MPLA and IFA tended to protect, and Poly(I:C), Alum-Poly(I:C), CFA, and eCFA significantly protected against tumor-growth. Across all adjuvants, tumor-protection correlated with the induction of highly activating IgG2(c/b) Abs and afucosylated (F0) IgG1 Abs, the latter showing up to 5% abundance. While all adjuvants transiently induced IgG1 F0 following initial immunization, Poly(I:C)- and eCFA-induced memory responses also generated IgG1 F0 after repeated antigen-exposure without adjuvants. Additionally, Poly(I:C)-induced tumor-protection was associated with high IgG2c/IgG1 ratios, high levels of IgG galactosylation and sialylation, and IFNγ-producing CD8 + Tc1-cells. Conversely, Ova-eCFA-induced tumor-protection was additionally associated with high levels of IgG across all subclasses, but low levels of galactosylation and sialylation, and CD8 + Tc17- and CD4 + Th17-cells. Accordingly, tumor protecting adjuvants may induce common but also different protecting programs. A tumor-antigen-specific IgG2a monoclonal (m)Ab protected against tumor-growth in both its de-galactosylated and galactosylated plus sialylated forms, suggesting common and possibly distinct protective mechanisms. Tumor-protection via serum transfer from Poly(I:C)-immunized mice depended more on NK-cells, whereas eCFA-induced and non-sialylated/non-galactosylated mAbs promoted neutrophil activation. These findings may help to improve tumor vaccination protocols.