Prime-boost protein subunit vaccines against SARS2 CoV-2 are highly immunogenic in mice and macaques

In this preprint, the authors present their data comparing the efficacy and immunogenicity of both homologous and heterologous prime-boost vaccination of mice and macaques with either a viral spike (S) or a RBD subunit vaccine.  S vaccines elicited superior immunogenicity in mice and comparable responses to RBD vaccination in macaques.   Study highlights the potential of using recombinant spike protein as a vaccine candidate and highlights key differences in vaccine responses between mice and macaques. 

Research Highlights  

1. In mice, serum antibody titres, and GC B Cell and TFH cell responses are markedly improved with a single immunization of S rather than RBD 

2. Homologous (RBD-RBD or S-S) or heterologous (RBD-S or S-RBD) prime boost vaccination of mice, elicited poor immunogenic responses if S was not included in the vaccination strategy.  

3. Homologous (RBD-RBD or S-S) and heterologous (S-RBD) vaccination of macaques, elicited comparable immunogenic responses with all vaccine strategies utilized. 

4. A comparison of serum and neutralizing Ab titres revealed that responses to vaccination in mice far exceed those observed in convalescent Covid patients*see limitation below. 

Impact for COVID-19 research:  

• Provides evidence that the immunological response to vaccination can be improved by including the spike protein alongside the RBD. 

• Demonstrates the differences in the immunological response between mouse and non-human primates to the same vaccine-strategy, with particular reference to the differing VH gene usage and how this impacts on the generation of B cell responses post vaccination.  

Methodologies: 

• Study Type: In vivo (mouse and NHP). 

• Important cell lines/viral models used: Vaccine study 

• Key Techniques: Flow cytometric analysis of S and RBD-specific B cells and TFH cells, BCR sequencing, ACE2-RBD inhibition ELISA.  

Limitations: 

• As with all macaques studies the numbers are small, however, it is difficult to draw firm conclusions with a N of 2.  Furthermore, the presentation of data in Figure 3 is particularly difficult to interpret for some of the panels. 

• There are differences between the vaccine approaches used in the mice and macaques and this is not discussed by the authors.  A vaccination dose-response, at least in mice should have been considered.  

• In the macaque model, the RBD-S prime-boost vaccine has not been studied and the authors provide no explanation as to why. 

• The patients recruited for the convalescent and B Cell studies, are mainly mild infections, but do include some severe individuals, would have been useful to highlight the severe patients in Figure 4.