Abstract
Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice. After challenging the vaccinated animals at month 8 with H3N2 viruses, the cVLP group also demonstrated strong recall responses. On day 4 post-challenge, we measured increased antibody levels, ASCs and HAI titers with reduced viral load and inflammatory responses in the cVLP group. The animals vaccinated with the cVLP showed 20% cross-protection against drifted (Philippines) and 60% protection against homologous (Aichi) H3N2 viruses. Thus, the results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups.
Highlights
Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics
Sera and mucosal washes were collected at different time-points up to month 8 after booster immunization and the resulting Aichi virus-specific IgG and IgA antibody responses were analyzed by enzyme-linked-immunosorbent assay (ELISA)
The IgA levels were maintained throughout the study, suggesting the animals immunized with chimeric Virus-like particles (VLPs) (cVLPs) formulations generated potent long-lived mucosal immunogenicity (Fig. 1B–D)
Summary
Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. We examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. The results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups. The success of current influenza vaccine campaigns depends heavily on a more scalable platform with low cost that can induce long-term cross-protective immunity. Successful vaccines against influenza rely on the generation of long-lasting antibodies that are able to rapidly neutralize an invading virus and prevent infection in immunized individuals. The current challenge in influenza vaccine design is to induce long-lasting cross-protective immune responses against homologous, drifted, or shifted strains. Influenza vaccines that can elicit efficient cross-protection with the induction of memory cells and neutralizing antibodies may protect humans effectively from subsequent influenza infections
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