Protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant

Abstract

Chitin in the form of microparticles (chitin microparticles, CMP) has been demonstrated to be a potent stimulator of macrophages, promoting T-helper-1 (Th1) activation and cytokine response. In order to examine the mucosal adjuvant effect of CMP co-administered with influenza hemagglutinin (HA) vaccine against influenza infection, CMP were intranasally co-administered with influenza HA vaccine prepared from PR8 (H1N1) virus. Inoculation of the vaccine with CMP induced primary and secondary anti-HA IgA responses in the nasal wash and anti-HA IgG responses in the serum, which were significantly higher than those of nasal vaccination without CMP, and provided a complete protection against a homologous influenza virus challenge in the nasal infection influenza model. In addition, CMP-based immunization using A/Yamagata (H1N1) and A/Guizhou (H3N2) induced PR8 HA-reactive IgA in the nasal washes and specific-IgG in the serum. The immunization with A/Yamagata and CMP resulted in complete protection against a PR8 (H1N1) challenge in A/Yamagata (H1N1)-vaccinated mice, while that with A/Guizhou (H3N2) and CMP exhibited a 100-fold reduction of nasal virus titer, demonstrating the cross-protective effect of CMP and influenza vaccine. It is suggested that CMP provide a safe and effective adjuvant for nasal vaccination with inactivated influenza vaccine.

Induction of cross‐protective immunity against influenza A virus H5N1 by an intranasal vaccine with extracts of mushroom mycelia

“…Although these toxins effectively provoke mucosal immune responses, they elicit adverse clinical side effects, such as nasal discharge and the facial paralysis of Bell's palsy [Mutsch et al, 2004]. Therefore, other adjuvants that are both effective and safe for human use have been developed for clinical application with intranasal influenza vaccine [Coulter et al, 2003;Hasegawa et al, 2005;Ichinohe et al, 2005Ichinohe et al, , 2006Ichinohe et al, , 2007aAsahi-Ozaki et al, 2006].…”

Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant

“…Conventionally, inactivated influenza vaccines are administered by subcutaneous or intramuscular injection, with just live attenuated vaccines being administered by intranasal spray. However, non-invasive routes of inactivated influenza vaccine administration, including intranasal, sublingual, intradermal and pulmonary delivery have gained increasing attention Cuburu et al, 2007;Hasegawa et al, 2005;Quan et al, 2010). The pulmonary route is an attractive route given its non-invasive nature, ease of administration and lack of need for trained health care workers.…”

Mucoadhesive liposomes for intranasal immunization with an avian influenza virus vaccine in chickens

“…Many researchers have made efforts to improve antibody responses to antigens delivered mucosally. These include encapsulating the antigen into liposomes [4,5], nanoparticles [6], virosomes [7], and microparticles [8]. Surface modifications or coadministration with bioadhesive materials such as chitosan [9] have resulted in successful immune responses.…”