A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

Malonis, Ryan J.; Georgiev, George I; Haslwanter, Denise; VanBlargan, Laura A.; Fallon, Georgia; Vergnolle, Olivia; Cahill, Sean M.; Harris, Richard; Cowburn, David; Chandran, Kartik; Diamond, Michael S.; Lai, Jonathan R.

doi:10.1371/journal.ppat.1010573

Cited by 12 publications

(7 citation statements)

References 77 publications

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“…In another study, Choi et al developed a synthetic DNA vaccine consisting of POWV prM and envelope proteins, which elicited T cell and B cell immunity in mice and also protected the mice from POWV lethal challenge 19 . Additionally, an immunogen displaying the domain III of the envelope glycoprotein of POWV presented on self-assembling protein nanoparticle induced protective and neutralizing antibodies against POWV in mice 25 .…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatics and computational approaches driven designing a novel vaccine candidate against Powassan virus

Nguyen,

Kim

2024

Sci Rep

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Powassan virus (POWV) is an arthropod-borne virus (arbovirus) capable of causing severe illness in humans for severe neurological complications, and its incidence has been on the rise in recent years due to climate change, posing a growing public health concern. Currently, no vaccines to prevent or medicines to treat POWV disease, emphasizing the urgent need for effective countermeasures. In this study, we utilize bioinformatics approaches to target proteins of POWV, including the capsid, envelope, and membrane proteins, to predict diverse B-cell and T-cell epitopes. These epitopes underwent screening for critical properties such as antigenicity, allergenicity, toxicity, and cytokine induction potential. Eight selected epitopes were then conjugated with adjuvants using various linkers, resulting in designing of a potentially stable and immunogenic vaccine candidate against POWV. Moreover, molecular docking, molecular dynamics simulations, and immune simulations revealed a stable interaction pattern with the immune receptor, suggesting the vaccine's potential to induce robust immune responses. In conclusion, our study provided a set of derived epitopes from POWV’s proteins, demonstrating the potential for a novel vaccine candidate against POWV. Further in vitro and in vivo studies are warranted to advance our efforts and move closer to the goal of combatting POWV and related arbovirus infections.

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Section: Discussionmentioning

confidence: 99%

Immunoinformatics and computational approaches driven designing a novel vaccine candidate against Powassan virus

Nguyen,

Kim

2024

Sci Rep

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“…Nanoparticle (NP) vaccines were constructed using self-assembling Aquifex aeolicus lumazine synthase ( 57 ) fused to a next-generation SpyCatcher domain ( 54 , 58 , 59 ). To generate the NPs, a pET28a plasmid encoding an N-terminal 6-histidine tag, the Aquifex aeolicus lumazine synthase protein (UniProtKB entry O66529), and SpyCatcher003 ( 58 ) ( Table 1 ) was transformed into T7 Express E. coli and recombinant LumazineSynthase-SpyCatcher003 was expressed overnight at 18C.…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine

Bergeron,

Murray,

Juarez

et al. 2023

Front. Immunol.

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IntroductionRespiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.MethodsHere, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.ResultsThe results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.DiscussionThe results from this study support further NP-S177Q vaccine candidate development.

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“…The LS NP platform has been used in recent years to develop other viral vaccine candidates including MERS-CoV RBD [ 108 ], Powassan virus envelope protein domain III [ 109 ], pseudorabies virus glycoprotein D [ 159 ], IAV mini-HA, and extracellular domain of M2 [ 110 , 111 ], EBV gp350 [ 112 ], and the head domain (Gn, a target of neutralising antibodies) of Rift Valley fever virus glycoprotein [ 113 ]. Genetic fusion or tag coupling was used to link the viral antigens to the NP scaffold.…”

Section: Vaccine Platforms Utilising Various Pnpsmentioning

confidence: 99%

Protein Nanoparticles as Vaccine Platforms for Human and Zoonotic Viruses

Pandey,

Sahoo,

Pattnaik

2024

Viruses

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Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or live-attenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. Modern vaccines have evolved to contain purified antigenic subunits, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to these subunit vaccines. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present a repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterisation of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs, have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from human viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious viral diseases and enhancing vaccine efficacy and safety.

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A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

Cited by 12 publications

References 77 publications

Immunoinformatics and computational approaches driven designing a novel vaccine candidate against Powassan virus

Immunoinformatics and computational approaches driven designing a novel vaccine candidate against Powassan virus

Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine

Protein Nanoparticles as Vaccine Platforms for Human and Zoonotic Viruses

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