The COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a safe and effective vaccine a global priority. Cumulative evidence has shown that both B- and T-cell immunity contribute to the control of acute coronavirus infections. A major challenge is the development of long-lasting immune responses to the spike glycoprotein, the natural target of antibodies that can protect against natural viral infection. The design of the immunogen and the ability to establish effective memory B- and T-cell responses will be important for long-term protective immunity. In view of this, we have created supramolecular assemblies of SARS-CoV-2 spike (S), spike RBD, and nucleoprotein (NP) to generate virus-mimicking polyphosphazene assemblies (VMPAs), that can present antigens in multimeric and multivalent form to achieve a robust and neutralizing antibody and memory B- and T-cell responses required for protective immunity. Polyphosphazenes, such as poly[di(carboxylatophenoxy)phosphazene] (PCPP), have been extensively used as vaccine adjuvants. Analysis of immunized mice immunized with the VMPAs showed a significant enhancement of neutralizing antibody responses, particularly when spike was combined with NP in a VMPA, and also displayed increases in both CD4 and CD8 T cell responses. The cellular measure for long term efficacy of a vaccine is dependent on its ability to generate memory T cells, specifically central memory T cells that are able to self-renew and maintain antigen-specific effector cells anew. We find that the VMPA-adjuvanted antigen offered the greatest increase in the total pool of CD4 central memory cells. Taken together, these data demonstrate that the VMPA formulations elicit robust anti-spike antibody responses and prime measurable cellular immune responses in the vaccinated mice.

SARS-CoV-2 vaccine candidate based on virus-mimicking polyphosphazene assemblies

ACS Spring 2022

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