Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 induction is ideal for influenza

Sekiya, Toshiki; Mifsud, Edin; Ohno, Marumi; Nomura, Naoki; Sasada, Mayumi; Fujikura, Daisuke; Daito, Takuji; Shingai, Masashi; Ohara, Yuuki; Nishimura, Tomohiro; Endo, Masafumi; Mitsumata, Ryotarou; Ikeda, Tomio; Hatanaka, Hironori; Kitayama, Hiroki; Motokawa, Kenji; Sobue, Tomoyoshi; Suzuki, Saori; Itoh, Yasushi; Brown, Lorena E.; Ogasawara, Kunio; Kino, Yoichiro; Kida, Hiroshi

doi:10.1016/j.vaccine.2019.02.057

Cited by 17 publications

(23 citation statements)

References 41 publications

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“…In recent years, a variety of different forms of influenza vaccines have been investigated in an attempt to improve their ability to protect humans against influenza, and a number of studies have re-evaluated the use of WPV as a vaccine. The foundation for this follows reports that WPVs are more immunogenic than SVs or subunit vaccines, particularly in immunologically naïve humans and animals [ 14 , 15 , 16 , 17 , 18 , 19 ]. Importantly, the concerns about the high reactogenicity that have been reported to be associated with the use of WPVs are thought to be, in part, the result of residual egg-derived products carried through from the production process [ 20 ], which can now be lessened through the implementation of better purification techniques and/or the use of cell culture-based production systems [ 21 , 22 , 23 ].…”

Section: Currently Licensed Influenza Vaccinesmentioning

confidence: 99%

“…Several clinical trials have since reported a similar degree of reactogenicity of WPV to that of SVs [ 24 , 25 , 26 , 27 , 28 , 29 ], and some of these studies also reported higher seroconversion rates using lower doses of WPV compared to SV [ 24 , 25 , 28 ]. Furthermore, additional “dose-sparing” effects of WPV can be achieved in small animal models without [ 17 ], or with, adjuvants such as CoVaccine HT [ 30 ] or cationic lipid/DNA complexes [ 31 ]. These dose-sparing effects are thought to be due to (1) the particulate nature of WPV virions, which possess a higher density of antigenic proteins compared to detergent disrupted soluble antigens that make up a SV [ 16 ], and/or (2) the presence of viral RNA in WPV, which can signal through Toll-like receptor (TLR) 7 to potentially provide an adjuvant effect [ 32 , 33 ].…”

Section: Currently Licensed Influenza Vaccinesmentioning

confidence: 99%

“…The egg-derived vaccine viruses are highly purified using state-of-the-art technologies. When the immunogenicity of the WPVs were examined alongside the corresponding SVs in naïve mouse and macaque models [ 17 ], the results showed greater levels of hemagglutination-inhibiting antibodies, which led to protection from lethal homologous influenza virus challenge. These results with WPV were achieved using only one fifth of the HA dose of SV, an indication of substantial dose sparing.…”

Section: Revisited Whole Virus Particle Vaccine In Super-pure Formmentioning

confidence: 99%

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Selecting and Using the Appropriate Influenza Vaccine for Each Individual

Sekiya

Ohno

Nomura

et al. 2021

Viruses

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Despite seasonal influenza vaccines having been routinely used for many decades, influenza A virus continues to pose a global threat to humans, causing high morbidity and mortality each year. The effectiveness of the vaccine is largely dependent on how well matched the vaccine strains are with the circulating influenza virus strains. Furthermore, low vaccine efficacy in naïve populations such as young children, or in the elderly, who possess weakened immune systems, indicates that influenza vaccines need to be more personalized to provide broader community protection. Advances in both vaccine technologies and our understanding of influenza virus infection and immunity have led to the design of a variety of alternate vaccine strategies to extend population protection against influenza, some of which are now in use. In this review, we summarize the progress in the field of influenza vaccines, including the advantages and disadvantages of different strategies, and discuss future prospects. We also highlight some of the challenges to be faced in the ongoing effort to control influenza through vaccination.

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Section: Currently Licensed Influenza Vaccinesmentioning

confidence: 99%

Section: Currently Licensed Influenza Vaccinesmentioning

confidence: 99%

Section: Revisited Whole Virus Particle Vaccine In Super-pure Formmentioning

confidence: 99%

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Selecting and Using the Appropriate Influenza Vaccine for Each Individual

Sekiya

Ohno

Nomura

et al. 2021

Viruses

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“…For example, although inactivated whole-virion vaccines can generate strong adaptive immunity, they can cause inflammatory responses that might induce adverse reactions [ 4 ]. In contrast, although SVs alone evoke weaker B-cell and T-cell responses than inactivated whole-virion vaccines, SVs are very safe compared to whole-virion vaccines [ 1 , 4 ]. One means for improving the efficacy of SVs is to choose an appropriate adjuvant [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

et al. 2020

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Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared to other types. Here, we assessed the potential of the lipid nanoparticle (LNP) we developed as an adjuvant for conventional influenza SV as an antigen in mice. The LNP did not induce the production of cytokines such as interleukin-6 (IL-6) and IL-12 p40 by dendritic cells or the expression of co-stimulatory molecules on these cells in vitro. In contrast, an SV adjuvanted with LNP improved SV-specific IgG1 and IgG2 responses and the Th1 response compared to the SV alone in mice. In addition, SV adjuvanted with an LNP gave superior protection against the influenza virus challenge over the SV alone and was as effective as SV adjuvanted with aluminum salts in mice. The LNP did not provoke inflammatory responses such as inflammatory cytokine production and inflammatory immune cell infiltration in mice, whereas aluminum salts induced inflammatory responses. These results suggest the potential of the LNP as an adjuvant without inflammatory responses for influenza SVs. Our strategy should be useful for developing influenza vaccines with enhanced efficacy and safety.

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“…WPV formulations prepared by each manufacturer induced stronger neutralizing antibodies and innate immune responses in mice compared to SV formulations consisting of the same vaccine strains. In addition, WPV exhibited low pyrogenicity, thereby highlighting their potential for priming safe and effective immune responses in highrisk groups 25,26 .…”

Section: Introductionmentioning

confidence: 99%

Immunization with inactivated whole virus particle influenza virus vaccines induces superior immunity in cynomolgus macaques

Chua

Sekiya²,

Koutsakos

et al. 2022

Preprint

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Influenza viruses circulate globally, causing seasonal influenza outbreaks. Although antibody-inducing vaccines are the most effective way to combat seasonal infections, current vaccines can have poor efficacy, especially in children and immunocompromised individuals. We investigated the immunogenicity and efficacy of monovalent and quadrivalent formulations of the whole virus particle vaccine (WPV) in comparison to the commonly used split vaccines (SVs) in a non-human primate model. Naïve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV formulations consistently induced a stronger neutralizing antibody response against vaccine-matched virus strains, while reactogenicity was minimal. In contrast to the modest responses in SV-vaccinated animals, responses in WPV-primed animals were further increased by boosting with either formulation. Using a 28-parameter multiplex bead array to define key antibody features, we found that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV elevated IgG responses against A/H1N1 haemagglutinin (HA) and HA-Stem after each vaccine dose. Higher IgA responses to A/H1N1-HA were also induced after each WPV dose. Antibodies to A/H1N1-HA and HA-Stem that could engage FcγR2a and FcγR3a were present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. WPV-enhanced antibody responses were associated with higher frequencies of HA-reactive B-cells and IFN-γ-producing CD4+ T-cell responses. Our data suggest that robust antibody responses require WPV to be given as a priming dose but do not depend on the vaccine type used for the second dose. In contrast, antibody responses are not as prominent when SV is given first. Our findings support vaccination regimens using WPV, which may be particularly beneficial for priming immunologically-naïve individuals, such as the young and immunocompromised, and also advantageous in the event of a pandemic outbreak.

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Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 induction is ideal for influenza

Cited by 17 publications

References 41 publications

Selecting and Using the Appropriate Influenza Vaccine for Each Individual

Selecting and Using the Appropriate Influenza Vaccine for Each Individual

Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

Immunization with inactivated whole virus particle influenza virus vaccines induces superior immunity in cynomolgus macaques

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