Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial

Houser, Katherine V.; Chen, Grace L.; Carter, Cristina; Crank, Michelle C.; Nguyen, Thuy‐Ai; Florez, Maria Claudia Burgos; Berkowitz, Nina M.; Mendoza, Floreliz; Hendel, Cynthia S.; Gordon, Ingelise J.; Coates, Emily E.; Vazquez, Sandra; Stein, Judy; Case, Christopher L.; Lawlor, Heather; Carlton, Kevin; Gaudinski, Martin R.; Strom, Larisa; Hofstetter, Amelia R.; Liang, Chi-Hui; Narpala, Sandeep; Hatcher, Christian; Gillespie, Rebecca A.; Creanga, Adrian; Kanekiyo, Masaru; Raab, Julie E.; Andrews, Sarah F.; Zhang, Yi; Yang, Eun Sung; Wang, Lingshu; Leung, Kwanyee; Kong, Wing-Pui; Freyn, Alec W.; Nachbagauer, Raffael; Palese, Peter; Bailer, Robert T.; McDermott, Adrian B.; Koup, Richard A.; Gall, Jason; Arnold, Frank; Mascola, John R.; Graham, Barney S.; Ledgerwood, Julie E.

doi:10.1038/s41591-021-01660-8

Cited by 95 publications

(69 citation statements)

References 38 publications

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“…Together, these results demonstrate that immunogens lacking the immunodominant head domain can elicit a group-specific, hetero-subtypic immune response 293 , 294 . Recently, a ferritin nanoparticle-based vaccine incorporating the ectodomain of HA from an H2N2 pandemic strain was demonstrated to be safe and immunogenic in a phase I clinical trial, supporting its potential application in pandemic preparedness and universal influenza vaccine development 295 , 296 .…”

Section: Implications For Vaccine Developmentmentioning

confidence: 97%

Antibodies to combat viral infections: development strategies and progress

Pantaleo

Correia

Fenwick

et al. 2022

Nat Rev Drug Discov

104

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Monoclonal antibodies (mAbs) are appealing as potential therapeutics and prophylactics for viral infections owing to characteristics such as their high specificity and their ability to enhance immune responses. Furthermore, antibody engineering can be used to strengthen effector function and prolong mAb half-life, and advances in structural biology have enabled the selection and optimization of potent neutralizing mAbs through identification of vulnerable regions in viral proteins, which can also be relevant for vaccine design. The COVID-19 pandemic has stimulated extensive efforts to develop neutralizing mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several mAbs now having received authorization for emergency use, providing not just an important component of strategies to combat COVID-19 but also a boost to efforts to harness mAbs in therapeutic and preventive settings for other infectious diseases. Here, we describe advances in antibody discovery and engineering that have led to the development of mAbs for use against infections caused by viruses including SARS-CoV-2, respiratory syncytial virus (RSV), Ebola virus (EBOV), human cytomegalovirus (HCMV) and influenza. We also discuss the rationale for moving from empirical to structure-guided strategies in vaccine development, based on identifying optimal candidate antigens and vulnerable regions within them that can be targeted by antibodies to result in a strong protective immune response.

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Section: Implications For Vaccine Developmentmentioning

confidence: 97%

Antibodies to combat viral infections: development strategies and progress

Pantaleo

Correia

Fenwick

et al. 2022

Nat Rev Drug Discov

104

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show abstract

“…These nanocages showed an especially high level of protective efficiency compared to soluble antigen alone, with minimal risk of autoimmunity through genetic diversity from human ferritin [ 39 ]. Additionally, in a very recent phase 1 clinical trial study, no significant effect was found on hematologic parameters, including iron levels, hemoglobin levels, hematocrit, white blood cell counts, and neutrophil counts, after HPF nanocage-derived H2 influenza vaccination [ 29 ]. To take advantage of these characteristics, we designed three spike-protein-conjugated HPF nanocages, Wuhan-Hu-1, B.1.351, and B.1.429 plasmids, as immunogens.…”

Section: Resultsmentioning

confidence: 99%

“…Owing to the capacities that ferritin offers, ferritin nanocages have been proposed in many studies as vaccine platforms against different diseases, including cancer [ 21 , 22 , 23 ], various viruses [ 24 , 25 , 26 ], and other pathogens [ 27 ]. It has been shown that ferritin nanocages have lymph-node target ability, which makes them able to elicit efficient antigen delivery to antigen-presenting cells (APCs) [ 22 , 28 ], high immunogenicity [ 27 , 29 ], and stability [ 30 , 31 ]. Moreover, the structure of ferritin has the advantage of displaying various antigens by fusing to their surface [ 27 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

A Multivalent Vaccine Based on Ferritin Nanocage Elicits Potent Protective Immune Responses against SARS-CoV-2 Mutations

Kim

Kim²,

Kim³

et al. 2022

IJMS

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The SARS-CoV-2 pandemic has created a global public crisis and heavily affected personal lives, healthcare systems, and global economies. Virus variants are continuously emerging, and, thus, the pandemic has been ongoing for over two years. Vaccines were rapidly developed based on the original SARS-CoV-2 (Wuhan-Hu-1) to build immunity against the coronavirus disease. However, they had a very low effect on the virus’ variants due to their low cross-reactivity. In this study, a multivalent SARS-CoV-2 vaccine was developed using ferritin nanocages, which display the spike protein from the Wuhan-Hu-1, B.1.351, or B.1.429 SARS-CoV-2 on their surfaces. We show that the mixture of three SARS-CoV-2 spike-protein-displaying nanocages elicits CD4+ and CD8+ T cells and B-cell immunity successfully in vivo. Furthermore, they generate a more consistent antibody response against the B.1.351 and B.1.429 variants than a monovalent vaccine. This leads us to believe that the proposed ferritin-nanocage-based multivalent vaccine platform will provide strong protection against emerging SARS-CoV-2 variants of concern (VOCs).

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“…This “immunological imprint” introduces birth year-dependent bias in immune repertoire and may influence group preference of the vaccine-induced immunity, posing another layer of difficulty for achieving universal influenza immunity in humans 47 . Whether a designed vaccine can override and reprogram the imprinted group-biased immunity in humans remains to be determined, although there are vaccine candidates in advanced clinical trials that show some promise in phase 1 human clinical trials by eliciting the HA stem-directed antibody responses in adults with preexisting influenza immunity 48–50 . In addition, the building block of our stem-nanoparticles is encoded by a single gene and its assembly is precise and efficient, making it a candidate for genetic vaccine delivery approaches such as mRNA and recombinant viral vectors.…”

Section: Discussionmentioning

confidence: 99%

Vaccine-elicitation of cross-group neutralizing protective antibodies to influenza A viruses

Moin

Boyington

Boyoglu-Barnum

et al. 2022

Preprint

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Current influenza vaccines predominantly induce immunity to the hypervariable viral hemagglutinin (HA) head, requiring frequent vaccine reformulation. Conversely, antigenic sites on the conserved HA stem are subdominant and harbor a supersite which is targeted by broadly neutralizing antibodies (bnAbs), making it a prime target for universal vaccines. Here, we show that co-immunization of two stem immunogens derived from influenza A group 1 and 2 HAs elicits cross-group protective immunity and neutralizing antibody responses in mice, ferrets, and nonhuman primates (NHPs). Immunized mice were protected from multiple group 1 and 2 viruses, and all animal models showed broad serum neutralizing activity. A bnAb isolated from an immunized NHP broadly neutralized and conferred protection from viruses including H5N1 and H7N9. Genetic and structural analyses revealed a remarkable convergent evolution between macaque and human bnAbs, illustrating the biophysical constraints for acquiring immunoglobulins with cross-group specificity. Co-immunization of stem immunogens elicits not only group-specific protective immunity, but also cross-group bnAb responses, and represents a step towards broadly protective influenza vaccines.

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Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial

Cited by 95 publications

References 38 publications

Antibodies to combat viral infections: development strategies and progress

Antibodies to combat viral infections: development strategies and progress

A Multivalent Vaccine Based on Ferritin Nanocage Elicits Potent Protective Immune Responses against SARS-CoV-2 Mutations

Vaccine-elicitation of cross-group neutralizing protective antibodies to influenza A viruses

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