Development of a Modular NTA:His Tag Viral Vaccine for Co-delivery of Antigen and Adjuvant.

The SARS-CoV-2 pandemic has highlighted the need for vaccines that are effective, but quickly produced. Of note, vaccines with plug-and-play capabilities that co-deliver antigen and adjuvant to the same cell have shown remarkable success. Our approach of utilizing a nitrilotriacetic acid (NTA) histidine (His)-tag chemistry with viral adjuvants incorporates both of these characteristics: plug-and-play and co-delivery. We specifically utilize the cowpea mosaic virus (CPMV) and the virus-like particles from bacteriophage Qß as adjuvants and bind the model antigen ovalbumin (OVA). Successful binding of the antigen to the adjuvant/carrier was verified by SDS-PAGE, western blot, and ELISA. Immunization in C57BL/6J mice demonstrates that with Qß - but not CPMV - there is an improved antibody response against the target antigen using the Qß-NiNTA:His-OVA versus a simple admixture of antigen and adjuvant. Antibody isotyping also shows that formulation of the vaccines can alter T helper biases; while the Qß-NiNTA:His-OVA particle produces a balanced Th1/Th2 bias the admixture was strongly Th2. In a mouse model of B16F10-OVA, we further demonstrate improved survival and slower tumor growth in the vaccine groups compared to controls. The NiNTA:His chemistry demonstrates potential for rapid development of future generation vaccines enabling plug-and-play capabilities with effectiveness boosted by co-delivery to the same cell.

COVID-19 Vaccine Frontrunners and Their Nanotechnology Design.

Humanity is experiencing a catastrophic pandemic. SARS-CoV-2 has spread globally to cause significant morbidity and mortality, and there still remain unknowns about the biology and pathology of the virus. Even with testing, tracing, and social distancing, many countries are struggling to contain SARS-CoV-2. COVID-19 will only be suppressible when herd immunity develops, either because of an effective vaccine or if the population has been infected and is resistant to reinfection. There is virtually no chance of a return to pre-COVID-19 societal behavior until there is an effective vaccine. Concerted efforts by physicians, academic laboratories, and companies around the world have improved detection and treatment and made promising early steps, developing many vaccine candidates at a pace that has been unmatched for prior diseases. As of August 11, 2020, 28 of these companies have advanced into clinical trials with Moderna, CanSino, the University of Oxford, BioNTech, Sinovac, Sinopharm, Anhui Zhifei Longcom, Inovio, Novavax, Vaxine, Zydus Cadila, Institute of Medical Biology, and the Gamaleya Research Institute having moved beyond their initial safety and immunogenicity studies. This review analyzes these frontrunners in the vaccine development space and delves into their posted results while highlighting the role of the nanotechnologies applied by all the vaccine developers.

COVID-19 vaccine development and a potential nanomaterial path forward.

The COVID-19 pandemic has infected millions of people with no clear signs of abatement owing to the high prevalence, long incubation period and lack of established treatments or vaccines. Vaccines are the most promising solution to mitigate new viral strains. The genome sequence and protein structure of the 2019-novel coronavirus (nCoV or SARS-CoV-2) were made available in record time, allowing the development of inactivated or attenuated viral vaccines along with subunit vaccines for prophylaxis and treatment. Nanotechnology benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures. In fact, the first vaccine candidate launched into clinical trials is an mRNA vaccine delivered via lipid nanoparticles. To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufacturing and global distribution. Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnology and advanced manufacturing.