Engineered Nanoparticle Applications for Recombinant Influenza Vaccines

Sia, Zachary R; Miller, Matthew S.; Lovell, Jonathan F.

doi:10.1021/acs.molpharmaceut.0c00383

Cited by 17 publications

(11 citation statements)

References 137 publications

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“…Nanoparticles can be used as vaccine development systems to facilitate specific antigen delivery, and induce an efficient response from the immune system, comparable to virus‐based strategies (Sia et al, 2020; Sulczewski et al, 2018; Wang et al, 2018). Several formats are available, such as: polymeric, Inorganic, liposomes, immunostimulating complex (ISCOM), VLPs (discussed in detail in Section 2.2 to 3), self‐assembled proteins, and emulsions (Sia et al, 2020; Sulczewski et al, 2018). Furthermore, due to the protection of the applied antigen from enzymatic degradation, the bioavailability of the vaccine antigen can also be improved (Singh et al, 2017), being particularly advantageous for mucosal vaccination.…”

Section: Strategies For the Development Of Influenza Vaccinesmentioning

confidence: 99%

“…Due to the properties displayed by nanoparticles, there is a high potential for viral treatment. Nevertheless, there are still some technical issues to overcome, namely the loading of the required quantity of antigens into the particle, or the prevention of antigen denaturation during vaccine formulation, which are critical to improve vaccine safety and efficacy (Sia et al, 2020; Wang et al, 2018).…”

Section: Strategies For the Development Of Influenza Vaccinesmentioning

confidence: 99%

See 1 more Smart Citation

Downstream processing for influenza vaccines and candidates: An update

Carvalho

Peixoto

Carrondo

et al. 2021

Biotech & Bioengineering

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Seasonal and pandemic influenza outbreaks present severe health and economic burdens. To overcome limitations on influenza vaccines' availability and effectiveness, researchers chase universal vaccines providing broad, long-lasting protection against multiple influenza subtypes, and including pandemic ones.Novel influenza vaccine designs are under development, in clinical trials, or reaching the market, namely inactivated, or live-attenuated virus, virus-like particles, or recombinant antigens, searching for improved effectiveness; all these bring downstream processing (DSP) new challenges. Having to deal with new influenza strains, including pandemics, requires shorter development time, driving the development of faster bioprocesses. To cope with better upstream processes, new regulatory demands for quality and safety, and cost reduction requirements, new unit operations and integrated processes are increasing DSP efficiency for novel vaccine formats.This review covers recent advances in DSP strategies of different influenza vaccine formats. Focus is given to the improvements on relevant state-of-the-art unit operations, from harvest and clarification to purification steps, ending with sterile filtration and formulation. The development of more efficient unit operations to cope with biophysical properties of the new candidates is discussed: emphasis is given to the design of new stationary phases, 3D printing approaches, and continuous processing tools, such as continuous chromatography. The impact of the production platforms and vaccine designs on the downstream operations for the different influenza vaccine formats approved for this season are highlighted.

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Section: Strategies For the Development Of Influenza Vaccinesmentioning

confidence: 99%

Section: Strategies For the Development Of Influenza Vaccinesmentioning

confidence: 99%

Downstream processing for influenza vaccines and candidates: An update

Carvalho

Peixoto

Carrondo

et al. 2021

Biotech & Bioengineering

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“…Nanoparticle vaccine platform is one of the most promising innovative technologies for next-generation influenza vaccine development. [103][104][105][106] Nanoparticles can accommodate various vaccine components (proteins, peptides, DNA, mRNA, and molecular adjuvants) in a modular, tunable, and flexible way and facilitate the development of affordable vaccines by promoting logistically simplified vaccine manufacturing, storage, distribution, and administration. Tailored nanoparticle vaccines can program the induction of potent broadly protective immune responses and allow antigen dose-sparing.…”

Section: Nanotechnology Contributes To Next-generation Influenza Vacc...mentioning

confidence: 99%

Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

Dong

Wang

2021

Advanced NanoBiomed Research

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Influenza is one of the most severe and contagious respiratory infectious diseases. Influenza virus infection causes annual epidemics and occasional pandemics, resulting in an enormous health and economic burden worldwide. During the 2019-2020 flu season, the centers for disease control and prevention (CDC) estimates that flu caused 38 million illnesses, including 18 million medical visits, 405 000 hospitalizations, and 22 000 deaths in the United States. [1] Influenza viruses are enveloped RNA viruses of the Orthomyxoviridae family. Because the RNA polymerases lack the proofreading function, influenza viruses undergo constant antigenic drift and shift within animal and human reservoirs. [2] Influenza A viruses (IAVs) and influenza B viruses (IBVs) are the main circulating viruses that affect human health. So far, 18 hemagglutinin (HA) subtypes belonging to two HA phylogenetic groups and 11 neuraminidase (NA) subtypes have been identified for IAVs. [3] The IAVs H1N1 and H3N2 currently cause most epidemic diseases in humans. IBVs form a single antigenic group with two distinct lineages: Victoria and Yamagata.Seasonal vaccination is the most cost-effective method to combat influenza infection. However, current seasonal flu vaccines induce strain-specific immunity that rapidly wanes and displays low efficiencies against mismatched circulating strains and no effect on pandemics. The vaccines need annual reformulation based on the prediction by the WHO Global Influenza Surveillance and Response System to counter antigenic variations. [4] This uncertainty makes mismatches occur, resulting in suboptimal immunity. Fewer influenza cases occurred in the past 2020-2021 flu season in the United States than in any on record, [5] probably due to the widespread use of face masks and social distance to control COVID-19. The lack of exposure to the flu may make the population more susceptible to the virus when it returns. [6] Parallelly, predicting which strains will be circulating in the upcoming flu season and selecting vaccine manufacturing will be more challenging than ever.A next-generation universal influenza vaccine that elicits long-lasting cross-protective immunity against variant influenza strains will overcome the limitations of the current flu v accines. [7,8] Nanotechnology plays an indispensable role in the development of such vaccines. [9][10][11] Influenza viruses are nanosized particles enveloped by lipid membranes inserted with surface glycoprotein spikes. Nanoparticle vaccines can optimally mimic the influenza virus nanostructure with high antigen loads, facilitate targeted delivery and controlled antigen release, and synergize with molecular adjuvants to improve vaccine potency and breadth. Moreover, nanoparticle vaccines can facilitate rapid and scalable production, minimize cold-chain dependence, incorporate antigens in a flexibly modular fashion, and be affordably produced. Up to date, a variety of nanoparticle formulations have shown promising results in generating cross-reactive influenza immunity.

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“…Nanoparticle vaccine platforms have been applied for i.n. vaccine development in recent years (6,7). Nanoparticles serve as antigen and adjuvant carriers and immunostimulants themselves to enhance immune responses.…”

mentioning

confidence: 99%

Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains

Dong

Wang

Gonzalez

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Intranasal (i.n.) immunization is a promising vaccination route for infectious respiratory diseases such as influenza. Recombinant protein vaccines can overcome the safety concerns and long production phase of virus-based influenza vaccines. However, soluble protein vaccines are poorly immunogenic if administered by an i.n. route. Here, we report that polyethyleneimine-functionalized graphene oxide nanoparticles (GP nanoparticles) showed high antigen-loading capacities and superior immunoenhancing properties. Via a facile electrostatic adsorption approach, influenza hemagglutinin (HA) was incorporated into GP nanoparticles and maintained structural integrity and antigenicity. The resulting GP nanoparticles enhanced antigen internalization and promoted inflammatory cytokine production and JAWS II dendritic cell maturation. Compared with soluble HA, GP nanoparticle formulations induced significantly enhanced and cross-reactive immune responses at both systemic sites and mucosal surfaces in mice after i.n. immunization. In the absence of any additional adjuvant, the GP nanoparticle significantly boosted antigen-specific humoral and cellular immune responses, comparable to the acknowledged potent mucosal immunomodulator CpG. The robust immune responses conferred immune protection against challenges by homologous and heterologous viruses. Additionally, the solid self-adjuvant effect of GP nanoparticles may mask the role of CpG when coincorporated. In the absence of currently approved mucosal adjuvants, GP nanoparticles can be developed into potent i.n. influenza vaccines, providing broad protection. With versatility and flexibility, the GP nanoplatform can be easily adapted for constructing mucosal vaccines for different respiratory pathogens.

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Engineered Nanoparticle Applications for Recombinant Influenza Vaccines

Cited by 17 publications

References 137 publications

Downstream processing for influenza vaccines and candidates: An update

Downstream processing for influenza vaccines and candidates: An update

Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains

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