COVID-19 vaccines are being rolled out worldwide in an attempt to curb the pandemic through herd immunity. The vaccines approved for use so far solely target the Spike protein from SARS-CoV-2, and this is a growing cause for concern given the emergence of novel coronavirus variants that bear Spike mutations.
Emergence of Novel Variants Poses a Threat to Current Vaccine Strategy
The potency of the COVID-19 vaccines currently in use is measured via the presence of circulating neutralising antibodies in vaccinated individuals, and this is dependent upon CD4+ T cell responses.
For now, it appears that Spike carries sufficient immune reactivity via its B cell and CD4+ T cell epitopes to protect vaccinated individuals from SARS-CoV-2 infection. However, mutations within the SARS-CoV-2 genome can lead to the disappearance of B and T cell epitopes, yielding so-called escape variants with lower immunogenic footprints that may jeopardise the current Spike-based vaccine strategy. We have previously demonstrated reduced binding to the most common Caucasian HLA I molecule ( A*0201) for the D614G variant that rapidly spread throughout Europe last year.
At present, the South African variant, also known as 501.V2 or B.1.351, is of greatest concern as preliminary research data suggests that it is more contagious1 and less susceptible to neutralising antibodies present in the serum of recovering COVID-19 patients2,3. Emerging data from vaccine developers also indicates that B.1.351 is less susceptible to neutralising antibodies in vaccinated individuals compared to other variants that have circulated earlier during the pandemic.
While the role of neutralising antibodies in immunisation remains undisputed, research carried out during the pandemic has also highlighted the importance of CD8+ T cell responses, in particular for fighting severe cases of COVID-194. More recently, it has been suggested that SARS-CoV-2-specific T-cell responses might be a better readout for immunogenicity than neutralising antibodies5.
Vaccines Stimulate B and T Cell Immune Responses
Since the pandemic began, Immunitrack has acknowledged the importance of developing a vaccine that can stimulate humoral and T cell immune responses for long-lasting immunity. Over the past year, Immunitrack has undertaken several large projects and collaborations leveraging its in vitro epitope prediction technology to support vaccine development and immune monitoring in infected and recovered COVID-19 patients.
Collaboration with Genlab To Develop First African COVID-19 Vaccine
South African company Genlab recently revealed its plans to develop the first African COVID-19 vaccine. The vaccine strategy is based on a nano-engineered, attenuated, recombinant bacteria that can elicit highly specialised Typo I and Type III interferon immune responses that lead to antibody recruitment and cellular responses at the site of infection.
The developmental vaccine, known as Shantivax, is built on a bacterial platform that has demonstrated safety and will continuously stimulate the immune system to provide long-term protection against COVID-19. Shantivax carries a recombinant vector that bears constitutively active genes to direct the interferon immune responses mentioned above as well as a diverse array of conserved SAR-CoV-2 epitopes selected for their potency among the African population and low mutation risk.
In this collaboration with Genlab, Immunitrack will leverage its proprietary in vitro epitope prediction technology and extensive experience in identification and HLA-restriction of SARS-CoV-2 epitopes to identify potent HLA I and II-binding SARS-CoV-2 epitopes for the African population. To maximise potency and minimise the risk of escape variants, the selected epitopes will encompass regions of the 4 major proteins in SARS-CoV-2, namely the membrane protein, envelope protein, nucleocapsid protein and spike protein.
Immunitrack is founded upon world-leading academic research on MHC-epitope binding. Using our deep knowledge in this area, we have developed the proprietary epitope screening platform technology, NeoScreen®. NeoScreen® accurately assays the affinity and stability of MHC/epitope interactions, and the technology has the capacity to rapidly screen libraries with thousands of (neo-) epitopes for applications within immune-oncology, vaccine production, T cell therapies and immune monitoring.
GENLAB is a South African based biotechnology company that specialises in the development of immunotherapies that range from vaccines to stem cell and cellular-based therapies. GENLAB uses a systematic interdisciplinary approach to novel therapeutic discovery, which can be designed to elicit or amplify an appropriate immune response. Our approach aims to integrate the primary (innate) immune response with the secondary (adaptive) immune response.