Preclinical study reveals that combining CpG 1018 and alum enhances mucosal and systemic immunity against N2 influenza in mice, suggesting optimal protection via nasal delivery.
Key Points
To assess the immunogenicity, cellular profile, and protective efficacy of an engineered N2 recombinant neuraminidase vaccine adjuvanted with CpG 1018 and alum across intramuscular and intranasal prime-boost regimens.
Immunized mice with an engineered N2 neuraminidase construct (N2-MPP) formulated with the TLR9 agonist CpG 1018 and alum using intramuscular and intranasal prime-boost combinations.
Profiled systemic cross-reactive neuraminidase-inhibiting antibodies, mucosal IgA titers from nasal washes and broncho-alveolar lavage fluids, and splenic and pulmonary CD4+ T-cell responses.
Evaluated viral clearance, lung tissue inflammation, and cross-protection following homologous and within-subtype (N2) influenza virus challenges.
CpG 1018 and alum acted synergistically to elicit high serum titers of cross-reactive neuraminidase-inhibiting antibodies and induced strong mucosal IgA responses via intranasal prime and boost combinations.
Intranasal administration drove lung tissue-resident memory CD4+ T-cell accumulation, with CpG 1018 specifically required to generate polyfunctional IFNγ/TNFα/IL-2-producing memory T cells.
The combination adjuvant accelerated viral clearance across prime-boost regimens, achieved sterilizing immunity upon homologous challenge with intranasal delivery, and conferred superior within-subtype cross-protection compared with intramuscular vaccination.