The unprecedented progression of the global Covid-19 vaccine rollout has demonstrated the capacity vaccines have to reduce Covid-19 disease burden and deaths. The increasing number of emerging variants, however, may impact disease transmission and the ability of vaccines to avert serious illness. This emphasises the importance of examining a variety of approaches alongside the current vaccine rollout. This briefing examines various preventative and therapeutic candidates in development that incorporate vector-based approaches for Covid-19 in clinical trials.

Sorrento Therapeutics ‘ pipeline candidates are being targeted against Covid-19 and utilise plasmid DNA for the production and purification of antibodies in Chinese hamster ovary (CHO) cells. The company is developing COVI-AMG, a monoclonal antibody that aims to bind to the SARS-CoV-2 spike protein to neutralise it from binding to the host. COVID-AMG has an intravenous route of administration, and its highest development stage is Phase II. The company is also developing Covidrops , the intranasal formulation of COVI-AMG.

Shenzhen Geno-Immune Medical Institute is developing two vaccine candidates that utilise a lentivirus vector, LV SMENP DC and Covid-19 aAPC Vaccine. LV SMENP DC has an intravenous and subcutaneous route of administration, while Covid-19 aAPC can only be administered subcutaneously. Lentivirus vectors are a type of retroviral vector that enables long-term expression and displays superior efficiency relative to non-viral vectors. The primary drawbacks for retroviral vectors, however, are their safety profiles, as significantly higher levels of mutagenicity have been observed in them. LV SMENP DC has progressed to Phase II status, while Covid-19 aAPC is currently in Phase I trials.

Altimmune is developing T-COVID, an intranasal immune modulating therapeutic based on the replication-deficient adenovirus 5 (RD-Ad5) vector platform, which typically induces a strong immunogenic response. The candidate has progressed to Phase II clinical trials, but sponsors have reported recruitment difficulties in the final cohort due to a decline in the incidence of disease following Covid-19 vaccine efforts.

TC BioPharm is currently developing TCB-008, a gene-modified cell therapy with an intravenous bolus route of administration. The candidate was previously designated for oncology indications, but its development has been inactive for the last two years. TCB-008 is now being repurposed for Covid-19. It produces a stimulatory effect on the immune system. TCB-008 is based on a lentivirus vector, with Phase II initiation planned in the coming weeks.

Products utilising viral vectors have been historically associated with a significant level of cytotoxic and mutagenic properties. As such, clinical trials are essential determinants of candidates’ safety profiles, particularly as Covid-19 therapeutics have the potential to be administered to a wide variety of individuals therefore potential risks must be averted. As highlighted in Table 1, the majority of vector-based candidates utilise lentivirus vectors in Covid-19 clinical trials.