Adjuvanted inactivated influenza A(H3N2) vaccines induce stronger immunogenicity in mice and confer higher protection in ferrets than unadjuvanted inactivated vaccines

Ann, Julie; Samant, Mukesh; Rhéaume, Chantal; Dumas, Carole; Beaulieu, Édith; Morasse, Audrey; Mallett, Corey P.; Hamelin, Marie‐Ève; Papadopoulou, Barbara; Boivin, Guy

doi:10.1016/j.vaccine.2014.08.029

Cited by 14 publications

(13 citation statements)

References 28 publications

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“…Clinical trials with proteosome-adjuvanted either monovalent H1N1 or trivalent inactivated vaccines have shown that proteosome-adjuvanted vaccines are well-tolerated, while inducing significantly higher serum HI and mucosal secretory IgA titers as compared to unadjuvanted vaccines [18][19][20]. Preclinical studies using Protollin-adjuvanted H3N2 vaccines also showed the similar results [14,21] Consistent with this, our data showed that Protollin-adjuvanted H5N1 vaccine induced significantly higher levels of mucosal IgA antibodies against A/VN/1203/04 virus both in nasal washes and lung, with considerable dose-sparing effect. The breadth of the mucosal IgA response was extended against clade 2 virus, A/IN05/05, As a pre-pandemic vaccine formulation, cross-clade immunity is an important and desirable feature, because the current endemic H5N1 viruses continuously evolve in HA antigenicity through antigenic drift and reassortment, thus making it hard to predict which strain will cause a pandemic.…”

Section: Discussionmentioning

confidence: 76%

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

Cao

Kim

Reber

et al. 2017

Vaccine

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Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing.

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Section: Discussionmentioning

confidence: 76%

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

Cao

Kim

Reber

et al. 2017

Vaccine

View full text Add to dashboard Cite

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“…In recent years, numerous studies have demonstrated the establishment of functional influenza- virus-specific CD8+ and CD4+ T cells after both intranasal and intramuscular immunization with IIV (Wang et al, 2015; Keijzer et al, 2014; Ann et al, 2014). It would therefore also be important to reconsider the genome composition of reassortant viruses for IIVs.…”

Section: Discussionmentioning

confidence: 99%

Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model

et al. 2017

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This study sought to improve an existing live attenuated influenza vaccine (LAIV) by including nucleoprotein (NP) from wild-type virus rather than master donor virus (MDV). H7N9 LAIV reassortants with 6:2 (NP from MDV) and 5:3 (NP from wild-type virus) genome compositions were compared with regard to their growth characteristics, induction of humoral and cellular immune responses in mice, and ability to protect mice against homologous and heterologous challenge viruses. Although, in general, the 6:2 reassortant induced greater cell-mediated immunity in C57BL6 mice than the 5:3 vaccine, mice immunized with the 5:3 LAIV were better protected against heterologous challenge. The 5:3 LAIV-induced CTLs also had better in vivo killing activity against target cells loaded with the NP366 epitope of recent influenza viruses. Modification of the genome of reassortant vaccine viruses by incorporating the NP gene from wild-type viruses represents a simple strategy to improve the immunogenicity and cross-protection of influenza vaccines.

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“…AS03 has been successfully used to enhance the efficacy, immunogenicity, and crossprotection of pandemic influenza vaccines. Recently, the adjuvant formulation AS25 (AS03, MPL) was shown to induce greater immunogenicity for the influenza vaccine than AS03 [33]. Another combination adjuvant, AS04, is approved for use with hepatitis B virus (HBV) and human papilloma virus (HPV) vaccines.…”

Section: Discussionmentioning

confidence: 99%

An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice

Lim

Lee

et al. 2017

PLoS ONE

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Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later. EV71-specific antibodies and neutralizing antibodies were induced and maintained until the end of the experimental period in all vaccinated groups. To determine the effectiveness of adjuvant for the EV71 vaccine, three adjuvants, i.e., aluminium hydroxide gel, monophosphoryl lipid A, and polyinosinic-polycytidylic acid, were administered separately with the FI-EV71 vaccine to mice via the intramuscular route. Mice administered the FI-EV71 vaccine formulated with all three adjuvants induced a significantly increased antibody response compared with that of the single adjuvant groups. The vaccinated group with triple adjuvants exhibited more rapid induction of EV71-specific and neutralizing antibodies than the other groups. These results suggested that the role of adjuvant in inactivated vaccine was important for eliciting effective immune responses against EV71. In conclusion, our results showed that FI-EV71 was a potential candidate vaccine for prevention of EV71 infection.

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Adjuvanted inactivated influenza A(H3N2) vaccines induce stronger immunogenicity in mice and confer higher protection in ferrets than unadjuvanted inactivated vaccines

Cited by 14 publications

References 28 publications

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model

An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice

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