Co-delivery of GPI-anchored CCL28 and influenza HA in chimeric virus-like particles induces cross-protective immunity against H3N2 viruses

Mohan, Teena; Kim, Jongrok; Berman, Zachary; Wang, Shelly; Compans, Richard W.; Wang, Bao‐Zhong

doi:10.1016/j.jconrel.2016.05.021

Cited by 13 publications

(29 citation statements)

References 75 publications

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“…These various physical and biological assays showed the integration and functional stability of HA and CCL28 in the VLPs. The results confirmed high incorporation of respective proteins with their functional stabilized structure in the VLPs31. Our vaccine strategy was to incorporate Aichi HA and GPI-CCL28 as antigen and adjuvant respectively into the same cVLP structure capable of delivering both components to the same cells, potentially enhancing antigen-specific immunogenicity.…”

Section: Methodssupporting

confidence: 58%

“…In the current study, we demonstrated that influenza VLP vaccines containing GPI-anchored CCL28 induced long-lasting protective immunity against infection with either homologous or heterologous H3N2 viruses. Our previous study also showcased that GPI-anchored CCL28 in influenza VLPs act as a strong adjuvant/immunostimulator at systemic and mucosal sites when immunized in mice via the intranasal route31. Thus, the capability for inducing long-lived protective immunity would be an important added strength to this approach.…”

Section: Discussionmentioning

confidence: 89%

“…The GPI-anchored CCL28 gene was constructed with the fusion of honeybee melittin and murine CD59 GPI-anchor as described previously31. M1, HA/M1, and cVLPs containing HA and M1 proteins derived from influenza Aichi virus co-incorporated with GPI-anchored CCL28 were produced using a recombinant baculoviruses (rBV) expression system47.…”

Section: Methodsmentioning

confidence: 99%

“…Total CCL28 and HA content in the produced VLPs were estimated by a quantitative ELISA using recombinant CCL28 (Prospoec, Brunswick, NJ, USA), and Aichi HA (Sino Biological Inc., North Wales, PA, USA) as the calibration standards, respectively. The biological activities of HA protein and CCL28 in VLPs were determined by hemagglutination assay and in vitro chemotactic activity towards the cells expressing CCR3 and CCR10 chemokine receptors, as described previously31. These various physical and biological assays showed the integration and functional stability of HA and CCL28 in the VLPs.…”

Section: Methodsmentioning

confidence: 99%

“…Because of its specific role in orchestrating the localization of IgA ASCs at mucosal sites, we previously analyzed the adjuvanticity of GPI-anchored CCL28 co-incorporated into influenza VLPs. We demonstrated that GPI-CCL28 in influenza VLPs acts as a strong immunostimulator at both systemic and mucosal sites, boosting significant cross-protection in animals against heterologous viruses across a large distance31.…”

mentioning

confidence: 96%

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Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses

Mohan

Berman

Luo

et al. 2017

Sci Rep

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Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice. After challenging the vaccinated animals at month 8 with H3N2 viruses, the cVLP group also demonstrated strong recall responses. On day 4 post-challenge, we measured increased antibody levels, ASCs and HAI titers with reduced viral load and inflammatory responses in the cVLP group. The animals vaccinated with the cVLP showed 20% cross-protection against drifted (Philippines) and 60% protection against homologous (Aichi) H3N2 viruses. Thus, the results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups.

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Section: Methodssupporting

confidence: 58%

Section: Discussionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

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Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses

Mohan

Berman

Luo

et al. 2017

Sci Rep

Self Cite

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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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Applications of chemokines as adjuvants for vaccine immunotherapy

et al. 2018

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Vaccinations are expected to aid in building immunity against pathogens. This objective often requires the addition of an adjuvant with certain vaccine formulations containing weakly immunogenic antigens. Adjuvants can improve antigen processing, presentation, and recognition, thereby improving the immunogenicity of a vaccine by simulating and eliciting an immune response. Chemokines are a group of small chemoattractant proteins that are essential regulators of the immune system. They are involved in almost every aspect of tumorigenesis, antitumor immunity, and antimicrobial activity and also play a critical role in regulating innate and adaptive immune responses. More recently, chemokines have been used as vaccine adjuvants due to their ability to modulate lymphocyte development, priming and effector functions, and enhance protective immunity. Chemokines that are produced naturally by the body's own immune system could serve as potentially safer and more reliable adjuvant options versus synthetic adjuvants. This review will primarily focus on chemokines and their immunomodulatory activities against various infectious diseases and cancers.

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Co-delivery of GPI-anchored CCL28 and influenza HA in chimeric virus-like particles induces cross-protective immunity against H3N2 viruses

Cited by 13 publications

References 75 publications

Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses

Chimeric virus-like particles containing influenza HA antigen and GPI-CCL28 induce long-lasting mucosal immunity against H3N2 viruses

Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

Applications of chemokines as adjuvants for vaccine immunotherapy

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