Looking Beyond the Spike Protein for SARS-CoV-2 Vaccine Design

2020, the year in which SARS-CoV-2 swept across the globe and plunged humanity into a global pandemic, is slowly drawing to a close. COVID-19 cases have started to climb once more in various corners of the world and the pressing question continues to be: When will we have a vaccine? The answer remains somewhat unclear. A long list of vaccines are now in human clinical trials for COVID-19, but for many, it is still early days and a long road of rigorous testing lies ahead, to ensure their safety and efficacy.

Biotech company COVAXX is developing a COVID-19 vaccine using a multi-antigen peptide platform, which not only targets the infamous SARS-CoV-2 Spike (S) protein but also targets other parts of the virus to enhance the immune response. The vaccine – UB-612 – recently entered a Phase 1 human clinical trial in Brazil. In this industry insight, Technology Networks spoke with Mei Mei Hu, co-founder of COVAXX, to learn more about the vaccine platform and the preclinical data that has been obtained for UB-612. Hu also provides an honest timeframe for the future development and deployment of UB-612.

Laura Lansdowne (LL): Could you elaborate on the design and mechanism of the UB-612 vaccine?

Mei Mei Hu (MMH): UB-612 is composed of an Fc-fusion protein and synthetic peptides that are designed to mimic functional viral epitopes of SARS-CoV-2. This allows for the inclusion and presentation of multiple epitopes to elicit both B-cell (antibody) and T-cell (cellular) immune responses. While it elicits functional neutralizing antibodies against the S protein receptor binding domain (RBD), it also employs additional epitopes from the M, N and S proteins, which provides an enhanced immune response. Classically most vaccines were produced using live or attenuated microorganisms, or parts of them, which can constitute a biohazard risk. As it is composed of synthetic peptides, rather than derived from a live virus, the UBITh Vaxxine Platform does not present a biohazard risk of mutation, or reversion of produced vaccines, and little or no risk of contamination by pathogenic or toxic substances.

LL: What are the benefits of using a multi-antigen peptide platform approach? How does this approach achieve greater efficacy?

MMH: At COVAXX we are using a high precision, multi-antigen peptide platform approach to develop a SARS-CoV-2 vaccine against COVID-19. This platform has been used successfully to develop a vaccine for foot and mouth disease, commercialized in billions of doses, and has previously been shown to be safe and well-tolerated in four human clinical trials in patients for other diseases such as Alzheimer's disease and Parkinson's disease. These include showing high immunogenicity in elderly patients as we know that this is especially important in terms of COVID-19, as older adults are one of the most vulnerable populations. We spent several months testing over 30 constructs for different properties, which we narrowed down to our lead vaccine candidate for COVID-19, UB-612, that we’re very confident in.

We’re not just targeting the S protein – we’re also targeting other parts of SARS-CoV-2 as well. We have seen the super heterogeneous response from serology samples, both in the field and our own, and we know that individuals respond very differently. There are different parts of the virus, not just the S protein, that are responsible for generating a protective immune response, and we have made sure that we target these epitopes in our vaccine design.

Image credit: COVAXX.

LL: Can you share your preliminary findings from preclinical studies of UB-612?

MMH: Our preliminary, preclinical studies suggest that our vaccine could lead to broad immunogenicity and could produce high neutralizing titers against the live coronavirus, SARS-CoV-2. Preclinical data in guinea pigs demonstrated that the COVAXX vaccine candidate generates anti-S1-RBD titers of > 1,000,000 as measured by Enzyme-Linked Immunosorbent Assay (ELISA), and neutralizing titers (100% neutralization as high as 32,000) in Cytopathic Effect (CPE) assays. We elicited a good T-cell response as well with a Th1 bias.

Molly Campbell (MC): Can you tell us more about the Phase II/III safety and efficacy study in Brazil

MMH: In September, we announced a partnership with Dasa, the largest diagnostic medicine company in Brazil and Latin America, and its affiliate Mafra, a major private vaccine distributor, to conduct a large scale human efficacy clinical trial in Brazil evaluating UB-612 against COVID-19.

Under the agreement, we will provide Dasa with our vaccine candidate for a Phase 2/3 study in Brazil designed to assess the safety and efficacy of UB-612. The clinical trials will take place at public and private laboratories and hospitals and will be conducted by contract research organizations after approval by ANVISA, the Brazilian regulatory agency.

We also announced that the first healthy adult volunteers were safely dosed in our Phase 1, open-label dose-escalation study. This trial is currently enrolling 60 healthy male and female adults, from 20–55 years of age, in three groups of 20 subjects, and is partly supported by a grant from the Ministry of Health and Wellness in Taiwan.

MC: What strategies have helped COVAXX to develop a COVID-19 vaccine quickly under the pressures of the pandemic? What have been some of the key challenges?

MMH: COVAXX is collaborating at unprecedented levels. Our scientists are using every resource at their disposal to accelerate steps in vaccine development. One benefit is that we have substantial internal experience in terms of scaling up manufacturing, as our sister company manufactures 500 million vaccine doses a year and has manufactured five billion doses to date.

The fact that we control the manufacturing process and can scale and distribute quickly gives us resolve that our COVID-19 vaccine will be one of the first vaccines to be distributed all the way to the end patient. The fact that we can leverage existing distribution infrastructure and do not require below freezing temperature control allows us to deploy on a global basis.

However, we are facing challenges that come up both in the usual course of drug development and in the unique situation of COVID-19. Some unique examples include ensuring key vaccine components are available for production, such as vials and stoppers, and planning within a rapidly evolving regulatory environment across multiple agencies worldwide.

MC: A reoccurring question in the current climate is: "When will a COVID-19 vaccine be available?" Are you able to provide comment here from a COVAXX perspective?

MMH: We have heard reports that a vaccine candidate will be ready by the end of 2020. It is important to remember that there will not be one winner-takes-all COVID-19 vaccine. There are going to be a number of vaccines that are approved and go into the marketplace, and we're hoping to be one of the leaders in this space with a best-in-class vaccine that is available and easily distributable. COVAXX knows our platform and knows how to manufacture. It's not theoretical. That is why we believe that, even though we may not be the first into the clinic, we do have a roadmap to actually be able to deliver 100 million vaccines to subjects in 2021.

Mei Mei Hu was speaking to Molly Campbell and Laura Elizabeth Lansdowne, Science Writers for Technology Networks.