Abstract
Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.
Highlights
Seasonal influenza infections lead to severe morbidity and mortality in sensitive individuals, including small children and individuals with heart and respiratory disorders [1]
We investigated in detail how the anionic EndocineTM and the cationic adjuvants N3OA and N3OA with Sq (N3OASq) mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses compared to vaccine alone after intranasal immunization
Serological responses The serum antibody responses induced by the unadjuvanted vaccine and the vaccine in combination with each of the mucosal adjuvants were compared by Hemagglutination inhibition (HAI)
Summary
Seasonal influenza infections lead to severe morbidity and mortality in sensitive individuals, including small children and individuals with heart and respiratory disorders [1]. Administered influenza vaccines often induce local mucosal influenza-specific IgA (secretory IgA). Secretory-IgA has been shown to have cross reactive properties [10,11], so nasal vaccination inducing secretory-IgA may contribute to a broader immune response. A recent study confirmed that nasal IgA contributes to the efficacy of a nasally administered influenza vaccine [12]. These promising protective effects have been reported by others, such as nasal administration of the virus-like particle (VLP) H1N1 influenza vaccine that showed broad protective immunity in mice and ferrets against distant influenza strains [13], against which a non-adjuvanted parenteral vaccine failed to induce an immune response
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