Researchers develop broadly neutralizing SARS-CoV-2 ferritin nanoparticle vaccine

The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the continued need for next-generation vaccines that confer broad protection against COVID-19, scientists developed an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine. The results of its evaluation in nonhuman primates (NHPs) are have been released as a preprint on the bioRxiv* server.

The researchers observed that the SpFN vaccine’s high-dose (50 µg), given twice within a 28-day interval, induced: 1) a Th1-biased CD4 T cell helper response and 2) a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and 3) minimal decrement against variants of concern.

We found that SARS-CoV-2 antibody responses in animals vaccinated with high-dose SpFN were significantly higher than those generated by high doses of leading genetic vaccines.”

Ferritin is a naturally occurring, ubiquitous iron storage protein with unique architecture and surface properties; it self-oligomerizes into a 24-unit spherical particle. The three-fold axis symmetry of the resulting polymer makes it conducive to conjugation and display of antigens. Ferritin nanoparticles are used as nanomedicine for drug delivery, and in bioassays and molecular imaging.

Due to its immune potency as a vaccine platform, the ferritin vaccines have already advanced to phase 1 clinical trial to target multiple influenza strains. It is also highly promising with trimeric glycoproteins, such as SARS-CoV-2 Spike (S) protein.

The SARS-CoV-2 is coronated with the glycoprotein, Spike (S), consisting of two subunits S1 and S2. The virus attaches to the host cell via the binding of the receptor-binding domain (RBD) on the S protein to the ACE2 (angiotensin-converting enzyme 2).

Studies are indicative that to confer protective immunity against SARS-CoV-2, both neutralizing and non-neutralizing (some fraction at least) antibodies against S are necessary.

The most potent neutralizing antibodies are designed and directed against the RBD of the S protein. The study here explores further previous studies of SpFN immune potency in mice.

The researchers evaluated the SpFN immunogenicity and efficacy against viral replication and pathology in the airways and lungs of nonhuman primates (NHP). NHPs are a standard model for the preclinical evaluation of SARS-CoV-2 vaccines. Here they used 32 male and female specific-pathogen-free, research-naïve Chinese-origin rhesus macaques (age 3 - 7 years).

The researchers designed the Spike Ferritin Nanoparticle (SpFN) vaccine as a ferritin-fusion recombinant protein for expression as a nanoparticle. They used Army Liposomal Formulation QS21 (ALFQ) as an adjuvant.

The researchers demonstrated that the serum antibodies neutralize SARS-CoV-2 ten times more potently than most vaccines. Assessing the cell-mediated immunity, the researchers observed robust Th1 responses, and minimal Th2 and CD8+ T cell responses; however, the responses correlated strongly.

The researchers explored the memory response in these animals, looking for indicators such as 1) IL-21, a cytokine, secreted by follicular helper CD4+ T cells (Tfh), regulates the evolution of memory B cells; and 2) CD40L, a broad T cell activation marker, expressed on the surfaces of CD4+ T cells and Tfh cells, promoting B cell maturation through antibody isotype switching. The results indicated an engaged memory response to the SpFN vaccine.

While testing for the breadth of the immune response, the researchers found that the SpFN vaccine against two predominantly circulating SARS-CoV-2 variants of concern (VOC): B.1.1.7 and B.1.351 elicited potent activity. They discussed the results of the neutralizing assays and cellular immune responses against SARS-CoV-1.

SpFN’s potent and broad immunogenicity profile and resulting efficacy in NHPs support its utility as a candidate platform for SARS-like beta coronaviruses. ”

In conclusion, the researchers established that the SpFN vaccine-elicited collective immune response, is a robust and rapid reduction in replicating virus in the upper and lower airways of animals and resultant prevention of pulmonary pathology.

In this study, altogether, the immunologic potency and breadth and virologic and pathologic efficacy of SpFN in NHPs support its advancement to an evaluation in phase 1 clinical trial, the researchers concluded.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Ramya Dwivedi

Written by

Dr. Ramya Dwivedi

Ramya has a Ph.D. in Biotechnology from the National Chemical Laboratories (CSIR-NCL), in Pune. Her work consisted of functionalizing nanoparticles with different molecules of biological interest, studying the reaction system and establishing useful applications.

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