Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

Mallajosyula, Jyothi K.; Hiatt, Ernie; Hume, Steve; Johnson, A.A.; Jeevan, Trushar; Chikwamba, Rachel; Pogue, Gregory P.; Bratcher, Barry; Haydon, Hugh; Webby, Richard J.; McCormick, Alison A.

doi:10.4161/hv.27567

Cited by 47 publications

(51 citation statements)

References 50 publications

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“…A high-molecular-weight HA oligomer elicited the strongest antibody response, followed by the HA trimer, while the monomer showed minimal efficacy [28]. Interestingly enough, immunogenicity of a plant-made monomeric HA could be improved by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) that is not infectious in mammals [43]. In another study, recombinant H7 that contained a T4 trimerization domain to ensure trimer formation has induced protection in mice [20].…”

Section: Discussionmentioning

confidence: 99%

Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus

Pushko

Pujanauski

Sun

et al. 2015

Vaccine

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A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant approaches including hemagglutinin (HA) and virus-like particles (VLPs) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. While high immunogenicity of VLP vaccines has been attributed to the native conformation of HA arranged in the regular repeated patterns within virus-like structures, there is limited data regarding molecular organization of HA within recombinant HA vaccine preparations. In this study, the full-length recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9 cells. We showed that purified full-length rH7 retained functional ability to agglutinate red blood cells and formed oligomeric pleomorphic subviral particles (SVPs) of ~20 nm in diameter composed of approximately 10 HA0 molecules. No significant quantities of free monomeric HA0 were observed in rH7 preparation by size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs was confirmed in the mouse and ferret challenge models suggesting that SVPs can be used for vaccination against H7N9 virus.

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Section: Discussionmentioning

confidence: 99%

Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus

Pushko

Pujanauski

Sun

et al. 2015

Vaccine

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“…TMV is a plant virus that cannot infect animals cells, but has been shown to interact with and stimulate mammalian dendritic cells [21]. TMV-conjugate vaccines have demonstrated protection against challenge with Francisella tularensis [22], and Influenza H1N1 [23] and H5N1 [24]. Here we demonstrate that TMV-conjugated to LcrV and F1 conferred protection against lethal pneumonic challenge with Y. pestis.…”

Section: Introductionmentioning

confidence: 66%

“…TMV-F1 and TMV-LcrV conjugate vaccines were prepared as described previously [23], with minor modifications. Lysine modified TMV [25] was mixed at a 1:1 molar ratio with each antigen in 100 mM 2-( N -morpholino) ethanesulfonic acid and 500 mM NaCl solution at pH 6.…”

Section: Methodsmentioning

confidence: 99%

Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague

Arnaboldi

Sambir

D’Arco

et al. 2016

Vaccine

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Yersinia pestis, one of history’s deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague model. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a tobacco mosaic virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice.

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“…Based on their rapid, stable, consistent and scalable production, recombinant subunit vaccines have been proven an effective strategy for meeting the demands of a possible influenza pandemic [67]. Compared with other vaccine types, subunit vaccines maintain the highest safety profile by the absence of infectious viruses.…”

Section: Advancements In the Development Of Subunit Influenza Vaccmentioning

confidence: 99%

Advancements in the development of subunit influenza vaccines

Zhang

Zheng

et al. 2015

Microbes and Infection

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The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines.

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Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

Cited by 47 publications

References 50 publications

Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus

Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus

Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague

Advancements in the development of subunit influenza vaccines

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