Design of a broadly reactive Lyme disease vaccine

Kamp, Heather D.; Swanson, Kurtis J.; Wei, Ronnie R.; Dhal, Pradeep K.; Dharanipragada, Ram; Kern, Arthur B.; Sharma, Bijaya; Šíma, Radek; Hajdušek, Ondřej; Hu, Linden T.; Wei, Chih‐Jen; Nabel, Gary J.

doi:10.1038/s41541-020-0183-8

Cited by 54 publications

(59 citation statements)

References 43 publications

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“…Reassessing how we target the induction of B-cell immunity and improve associated T-cell response is the future of nanovaccines. The approaches discussed in this Review can also be applied to other infectious diseases, such as malaria 16 , Lyme disease 60 and potentially COVID-19. Several nanovaccine candidates are in development and in pre-clinical phases of testing against COVID-19.…”

Section: Review Article | Focusmentioning

confidence: 99%

Eliciting B cell immunity against infectious diseases using nanovaccines

2020

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Section: Review Article | Focusmentioning

confidence: 99%

Eliciting B cell immunity against infectious diseases using nanovaccines

2020

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“…Unlike nanoparticle platforms that require post-purification conjugation of an antigen to a carrier or scaffold, here spike functionalized nanoparticles were produced by transfecting a single plasmid encoding the spike fused to the ferritin subunit into mammalian cells. We built on existing work using ferritin nanoparticles to display other viral antigens for vaccine development (30)(31)(32)(33)(34)(35)(36) and designed nanoparticles displaying the SARS-Cov-2 spike ectodomain. Importantly, the two ferritin-based antigens that we designed (S-Fer and SΔC-Fer) expressed comparably to spike trimers (S-GCN4 and SΔC-GCN4) in mammalian cells ( Figure S1), indicating that fusing the spike to ferritin does not negatively impact protein production.…”

Section: Discussionmentioning

confidence: 99%

“…One such multimerization platform, Helicobacter pylori ferritin, has been used to display antigens from influenza ( 31 , 32 ), HIV-1 ( 33 , 34 ), and Epstein-Barr virus ( 30 ), among others ( 35 , 36 ). H. pylori ferritin self-assembles into 24-subunit particles with eight three-fold axes of symmetry ( 37 ).…”

Section: Introductionmentioning

confidence: 99%

A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

Chen

Zhang

Sanyal

et al. 2020

Preprint

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Development of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against COVID-19.

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“…With the escalating prevalence of LD occurring in the context of climate change, clinicians are increasingly likely to encounter Lyme carditis. Until a vaccine strategy can be refined, vector control measures and an appropriate index of suspicion on the part of clinicians will be essential in responding to this important complication of LD [24].…”

Section: Discussionmentioning

confidence: 99%

Chest palpitations in a teenager as an unusual presentation of Lyme disease: case report

et al. 2020

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Background The incidence of Lyme disease (LD) in North America has increased substantially in the past two decades. Concomitant with the increased incidence of infection has been an enhancement in the recognition of LD complications. Here, we report a case of Lyme carditis complicated by heart block in a pediatric patient admitted to our children’s hospital. What is unique about this case is that the complaint of chest palpitations is an infrequent presentation of LD, and what it adds to the scientific literature is an improved understanding of LD in the pediatric population. Case presentation The patient was a 16-year-old male who presented with the main concerns of acute onset of palpitations and chest pain. An important clinical finding was Erythema migrans (EM) on physical exam. The primary diagnoses were LD with associated Lyme carditis, based on the finding of 1st degree atrioventricular heart block (AVB) and positive IgM and IgG antibodies to Borrelia burgdorferi. Interventions included echocardiography, electrocardiography (EKG), and intravenous antibiotics. The hospital course was further remarkable for transition to 2nd degree heart block and transient episodes of complete heart block. A normal sinus rhythm and PR interval were restored after antibiotic therapy and the primary outcome was that of an uneventful recovery. Conclusions Lyme carditis occurs in < 5% of LD cases, but the “take-away” lesson of this case is that carditis can be the presenting manifestation of B. burgdorferi infection in pediatric patients. Any patient with suspected Lyme carditis manifesting cardiac symptoms such as syncope, chest pain, or EKG changes should be admitted for parenteral antibiotic therapy and cardiac monitoring. The most common manifestation of Lyme carditis is AVB. AVB may manifest as first-degree block, or may present as high-grade second or third-degree block. Other manifestations of Lyme carditis may include myopericarditis, left ventricular dysfunction, and cardiomegaly. Resolution of carditis is typically achieved through antibiotic administration, although pacemaker placement should be considered if the PR interval fails to normalize or if higher degrees of heart block, with accompanying symptoms, are encountered. With the rising incidence of LD, providers must maintain a high level of suspicion in order to promptly diagnose and treat Lyme carditis.

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Design of a broadly reactive Lyme disease vaccine

Cited by 54 publications

References 43 publications

Eliciting B cell immunity against infectious diseases using nanovaccines

Eliciting B cell immunity against infectious diseases using nanovaccines

A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

Chest palpitations in a teenager as an unusual presentation of Lyme disease: case report

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