, 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.

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.

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The COVID-19 pandemic highlights the need for platform technologies enabling rapid development of vaccines for emerging viral diseases. The current vaccines target the SARS-CoV-2 spike (S) protein and thus far have shown tremendous efficacy. However, the need for cold-chain distribution, a prime-boost administration schedule, and the emergence of variants of concern (VOCs) call for diligence in novel SARS-CoV-2 vaccine approaches. We studied 13 peptide epitopes from SARS-CoV-2 and identified three neutralizing epitopes that are highly conserved among the VOCs. Monovalent and trivalent COVID-19 vaccine candidates were formulated by chemical conjugation of the peptide epitopes to cowpea mosaic virus (CPMV) nanoparticles and virus-like particles (VLPs) derived from bacteriophage Qβ. Efficacy of this approach was validated first using soluble vaccine candidates as solo or trivalent mixtures and subcutaneous prime-boost injection. The high thermal stability of our vaccine candidates allowed for formulation into single-dose injectable slow-release polymer implants, manufactured by melt extrusion, as well as microneedle (MN) patches, obtained through casting into micromolds, for prime-boost self-administration. Immunization of mice yielded high titers of antibodies against the target epitope and S protein, and data confirms that antibodies block receptor binding and neutralize SARS-CoV and SARS-CoV-2 against infection of human cells. We present a nanotechnology vaccine platform that is stable outside the cold-chain and can be formulated into delivery devices enabling single administration or self-administration. CPMV or Qβ VLPs could be stockpiled, and epitopes exchanged to target new mutants or emergent diseases as the need arises.

Plant viral nanoparticle CPMV outperforms other icosahedral viruses as an in situ vaccine for cancer immunotherapy.