Single dose combination nanovaccine provides protection against influenza A virus in young and aged mice

Ross, Kathleen A.; Senapati, Sujata; Alley, Jessica; Darling, Ross; Goodman, Jonathan T.; Jefferson, Matthew; Uz, Metin; Guo, Baoqing; Yoon, Kyoung‐Jin; Verhoeven, David; Kohut, Marian L.; Mallapragada, Surya K.; Wannemuehler, Michael J.; Narasimhan, Balaji

doi:10.1039/c8bm01443d

Cited by 38 publications

(47 citation statements)

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“…PVA (Fig. [17][18][19] This work builds upon our previous studies by systematically studying the safety and biocompatibility of the PVA-modified PBC gels and demonstrates that these novel materials can be developed as adjuvants for next generation vaccines. 15 Like our PBC system, PVA has gelation capabilities, often achieved through γ-irradiation-induced cross-linking or successive freeze/thaw cycles.…”

Section: Introductionmentioning

confidence: 65%

“…This modified hydrogel has been shown in previous studies to have adjuvant-like properties as evidenced by the induction of robust antibody responses following immunization. [17][18][19] This work builds upon our previous studies by systematically studying the safety and biocompatibility of the PVA-modified PBC gels and demonstrates that these novel materials can be developed as adjuvants for next generation vaccines.…”

Section: Introductionmentioning

confidence: 78%

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Safety and biocompatibility of injectable vaccine adjuvants composed of thermogelling block copolymer gels

Adams

Senapati

Haughney

et al. 2019

J Biomedical Materials Res

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Injectable thermogelling polymers have been recently investigated as novel adjuvants and delivery systems for next generation vaccines. As research into natural and synthetic biocompatible polymers progresses, the safety and biocompatibility of these compounds is of paramount importance. We have developed cationic pentablock copolymer (PBC) vaccine adjuvants based on Pluronic F127, a thermogelling triblock copolymer that has been approved by the FDA for multiple applications, and methacrylated poly(diethyl amino)ethyl methacrylate outer blocks. These novel materials have been demonstrated to effectively create an antigen depot, minimally impact antigen stability, and enhance the immune response to antigens (i.e., adjuvanticity) in mice. In this work, we investigated the safety and biocompatibility of the parent triblock Pluronic gels and the cationic PBC gels in mice. Histological analysis showed no injection site reactions and no damage to the liver or kidneys was observed upon administering the block copolymer formulations. However, the subcutaneous injection of a thermogelling Pluronic solution induced increased levels of lipids in the blood, with no further deleterious effects observed from the addition of the cationic outer blocks. This hyperlipidemia resolved within 30 days after the administration of the Pluronic formulation. To mitigate this adverse effect, the vaccine adjuvant formulations were modified by adding poly(vinyl alcohol), which allowed gelation, while reducing the amount of Pluronic in the formulation. This modified formulation abrogated the observed hyperlipidemia and no adverse effects were observed in the serum through biomarker analysis or at the injection site (i.e., inflammation) in comparison to the responses induced by administration of saline or incomplete Freund's adjuvant. These studies provide a foundation to developing these gels as adjuvants for next generation vaccines. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1754–1762, 2019.

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Section: Introductionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 78%

Safety and biocompatibility of injectable vaccine adjuvants composed of thermogelling block copolymer gels

Adams

Senapati

Haughney

et al. 2019

J Biomedical Materials Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Besides generating protein nanoparticles from antigenic subunits, their expression and/or display on proteinaceous biomaterial scaffolds such as ferritin, encapsulin 51 and bacteriophage VLPs has also been utilized to achieve multivalent antigen display for enhanced immunogenicity [52][53][54] . And finally, subunit vaccines can constitute viral proteins incorporated in synthetic nanomaterials, protein cages and VLPs, which serve as adjuvants and/or delivery vehicles, in addition to conferring other benefits inherent to each nanocarrier platform [55][56][57] . For example, the influenza virus vaccine Crucell (Janssen, Johnson & Johnson) is a liposomal formulation that incorporates influenza protein haemagglutinin 58 .…”

Section: Review Article | Focusmentioning

confidence: 99%

COVID-19 vaccine development and a potential nanomaterial path forward

et al. 2020

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, a novel coronavirus (nCoV or SARS-CoV-2) belonging to the betacoronavirus family emerged 1,2. All human betacoronaviruses are unique from one another, however, they do share a certain degree of genetic and structural homology. SARS-CoV-2 genome sequence homology with SARS-CoV and MERS-CoV is 77% and 50%, respectively 3. In contrast to the relatively smaller outbreaks of SARS-CoV in 2002 and MERS-CoV in 2012, SARS-CoV-2 is exhibiting an unprecedented scale of infection, resulting in a global pandemic declaration of Coronavirus Infectious Disease (COVID-19) on 11 March 2020 by the World Health Organization (WHO). On 1 June 2020, the World Health Organization reported >6 million confirmed cases and 371 thousand deaths globally. Of note, during the 1918 influenza pandemic, more death was observed in the second phase of outbreak 4. Similar to influenza, COVID-19 harbours the potential to become a seasonal disease 5. The high infection rate, long incubation period, along with mild-to-moderate symptoms experienced by many, make COVID-19 a troubling disease. A vaccine is crucial, in particular because data indicate asymptomatic transmission of COVID-19 6-8. More than 10 years ago, scientists predicted the pandemic potential of the coronaviruses 9. And for the past 30 years, a once-per-decade novel coronavirus has pushed our public health system to the limit, with SARS-CoV-2 being the most severe. Despite the repeated warnings and discussion, the world was not prepared for this pandemic. The rapid development, distribution and administration of a vaccine to the global population is the most effective approach to quell this pandemic and the only one that will lead to a complete lifting of restrictions. Challenges include the vaccine design itself, but also its manufacture and global distribution; cold chain requirements present logistical and fiscal barriers to the availability of important, life-saving vaccines in resource-poor areas of the world. Innovating vaccine delivery platforms and devices to break cold chain limitations are therefore an efficient solution to safeguard potent vaccination for both wealthy and lower-income countries.

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“…We employed an aged mouse model that has been shown to recapitulate age-related changes in humans (12,13) including responses to influenza infection and vaccination (14,15). Several adjuvant formulations have been previously shown to increase protective efficacy of hemagglutinin (HA)based influenza vaccines in aged mice, but these formulations required use of complex preparation procedures and some included more than one dose of vaccine (16)(17)(18)(19). However, influenza vaccine is administered only once during the annual vaccination campaigns.…”

Section: Introductionmentioning

confidence: 99%

Combination of STING Pathway Agonist With Saponin Is an Effective Adjuvant in Immunosenescent Mice

2019

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There is an urgent need to improve protective responses to influenza vaccination in the elderly population, which is at especially high risk for adverse outcomes from influenza infection. Currently available inactivated vaccines provide limited protection, even when a 4-fold higher dose of the vaccine is administered. Adjuvants are often added to vaccines to boost protective efficacy. Here we describe a novel combination of an activator of the STING pathway, 2 ′ ,3 ′ -cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) with a saponin adjuvant, that we found to be highly effective in boosting protective immunity from vaccination in an aged mouse model. Using this combination with a subunit influenza vaccine, we observed that survival of vaccinated 20 month-old mice after lethal challenge increased from 0 to 20% with unadjuvanted vaccine to 80-100%, depending on the vaccination route. Compared to unadjuvanted vaccine, the levels of vaccine-specific IgG and IgG2a increased by almost two orders of magnitude as early as 2 weeks after a single immunization with the adjuvanted formulation. By analyzing phosphorylation of interferon regulatory factor 3 (IRF3) in cell culture, we provide evidence that the saponin component increases access of exogenous cGAMP to the intracellular STING pathway. Our findings suggest that combining a STING activator with a saponin-based adjuvant increases the effectiveness of influenza vaccine in aged hosts, without having to increase dose or perform additional vaccinations. This study reports a novel adjuvant combination that (a) is more effective than current methods of boosting vaccine efficacy, (b) can be used to enhance efficacy of licensed influenza vaccines, and (c) results in effective protection using a single vaccine dose.

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Single dose combination nanovaccine provides protection against influenza A virus in young and aged mice

Abstract: Combined polyanhydride nanoparticles and pentablock copolymer micelles provide protection against homologous challenge in aged mice.

Cited by 38 publications

References 54 publications

Safety and biocompatibility of injectable vaccine adjuvants composed of thermogelling block copolymer gels

Safety and biocompatibility of injectable vaccine adjuvants composed of thermogelling block copolymer gels

COVID-19 vaccine development and a potential nanomaterial path forward

Combination of STING Pathway Agonist With Saponin Is an Effective Adjuvant in Immunosenescent Mice

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