Immunologic characterization of a novel inactivated nasal mumps virus vaccine adjuvanted with protollin.

摘要

An inactivated, mucosal mumps virus (MuV) vaccine would address many of the problems associated with current live-attenuated formulations. Protollin (Prl)-based adjuvants (containing TLR2 and TLR4 ligands) are well-suited for nasal administration. We sought to develop an inactivated whole-virus nasal vaccine for MuV using the Prl adjuvant/delivery vehicle and to test tolerability and immunogenicity in a mouse model. BALB/c mice exhibited signs of transient reactogenicity (hunched posture, erect fur, weight loss <=10% of total body weight) following administration of intranasal MuV-Prl vaccines, though most of these manifestations resolved within 24 h. Compared to high-dose unadjuvanted vaccine (8 micro gMuV), administration of high-dose adjuvanted formulation (8 micro gMuV-Prl) induced greater MuV-specific serum IgG (3.26E6 ng/mL vs. 2.2E5 ng/mL, 8 micro gMuV-Prl vs. 8 micro gMuV, p<0.001) and mucosal IgA (128 ng/mL vs. 45 ng/mL, 8 micro gMuV-Prl vs. 8 micro gMuV, p<0.05). Serum IgG isotypes and splenocyte cytokine secretion induced by MuV-Prl suggested a predominant T helper cell (Th)1-type immune response. This response was characterized by: (1) >=four-fold increase of IgG2a levels compared to IgG1; and (2) high IL-2 (644 pg/mL)/IFN- gamma (228 pg/mL) and low IL-5 (31 pg/mL) secretion in MuV-restimulated splenocytes from animals receiving MuV-Prl formulations. MuV-Prl vaccination induced higher levels of serum antibodies capable of neutralizing MuV in vitro than MuV alone, particularly for high-dose 8 micro g formulations (357 neutralizing units (NU)/mL vs. 32 NU/mL, 8 micro gMuV-Prl vs. 8 micro gMuV, p<0.001). Thus, nasal MuV-Prl vaccines are fairly well-tolerated and highly immunogenic in mice.