11.3.3.2

VSV-Based COVID-19 Vaccine Candidates

In the race of COVID-19 vaccines, several rVSV-based vaccine candidates against

COVID-19 expressing the spike protein of SARS-CoV-2 are evaluated in pre-

clinical trials (University of Western Ontario, Canada; University of Manitoba,

Canada; Aurobindo Pharma, India; FBRI SRC VB VECTOR, Russia; and Israel

Institute for Biological Research/Weizmann Institute of Science, Israel) and clinical

trials (Table 11.3). The construct of rVSVInd-msp-SF-Gtc used in COVID-19 vac-

cine candidates is temperature-sensitive (VSVInd-GML mutant), which is avirulent

in vivo and shows reduced cytopathic effect in vitro at 37°C, but replicates well at

31°C [77]. This characteristic can increase the safety of rVSV for human use. The

rVSVInd-msp-SF-Gtc expressed the SARS-CoV-2 spike protein, the honeybee

melittin signal peptide, and the VSV-G transmembrane protein.

11.4

OVERALL CONCLUSION ON VECTORED VACCINES

In 2013, the WHO had informal consultations on the topic “Where are we with the

development of viral vectored vaccine?” [78] The response to this question years later

can be summarized in the following. In the case of AdV vectors, there are a number of

human and non-human primates AdV serotypes that have been evaluated in pre-

clinical and clinical trials, including HAd5, HAd26, HAd35, ChAd63, etc. Successful

applications have been achieved during the COVID-19 pandemic with the licensing

of vectored vaccines using HAd5, HAd26, and ChAdY25 serotypes. Vaccination

against colds provoked by the HAd4 and HAd7 in the U.S. army is delivered orally in

the form of tablets. There is also progress in developing orally delivered HAd4 with

the H5N1 avian strain, as illustrated by advanced clinical trials.

The recommendation from the WHO working group is that platforms should be

developed in the case of a pandemic situation. They called for the development of

novel vectors as potential platforms, evaluation of viral vectors in heterologous

prime-boost regimens, improvement on manufacturing technology toward con-

tinuous cell culture (e.g., poxvirus uses chicken fibroblasts that are generated each

time), and closer collaboration between veterinary and human vaccine developers.

“Live viral vectors that express heterologous antigens are being extensively

investigated in the development of novel vaccines and it is believed that these will

provide an optimum immune response toward the expressed antigen” is one of the

guidelines from the European Medical Agency underlining a solid trend in the

development of vectored vaccines [79].

Years later, large-scale convincing demonstrations have been achieved through

the successful COVID-19 vaccination of hundreds of millions of people worldwide

with the live vectored vaccines that eventually bring together all the components to

induce an appropriate immune response for broad protection.

REFERENCES

[1] S. A. Mendonca, R. Lorincz, P. Boucher, and D. T. Curiel, “Adenoviral vector

vaccine platforms in the SARS-CoV-2 pandemic,” NPJ Vaccines, vol. 6, no. 1,

p. 97, Aug. 2021, doi: 10.1038/s41541-021-00356-x

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Bioprocessing of Viral Vaccines