Phase 3 Trial of Vaxxinity’s COVID-19 Vaccine as a Heterologous Booster Advances

Vaxxinity’s COVID-19 vaccine UB-612 is advancing toward becoming a heterologous booster with enrollment in a Phase 3 clinical trial completed and initiation of a rolling submission to the Therapeutic Goods Administration in Australia for provisional approval.

The Dallas-based company expects to release topline immunogenicity data by the end of the year for the vaccine, which is the first multitope protein/peptide-based vaccine candidate for SARS-CoV-2, designed to activate both B and T-cell responses.

“The potential advantages include well-tolerated safety profile, longer durability, broad coverage across new mutations, and easier distributability,” Ulo Palm, MD, PhD, chief medical officer of Vaxxinity, told Contagion. “Our goal is to serve the underserved and ensure no one is left behind with a vaccine that we’d choose for our own loved ones.”

The announcement of a rolling submission for provisional approval in Australia follows a similar announcement in September of a rolling submission to the Medicines and Healthcare Products Regulatory Agency in the United Kingdom.

The phase 3 trial, which began earlier this year, is designed to compare the safety and immunogenicity of UB-612 as a heterologous booster dose with a homologous booster with the same vaccine used in the primary series. The study includes about 1000 participants aged 16 and older who have received a primary series of vaccines from Oxford-AstraZeneca, Pfizer-BioNTech, Sinopharm or Sinovac.

Phase 1 and 2 trials of UB-612, which included about 4,000 participants, showed the vaccine was well-tolerated with no serious vaccine-related adverse events and elicited antibody titers comparable to authorized vaccines.

Early studies showed a booster dose of the vaccine increased neutralizing antibody levels against ancenstral SARS-CoV-2 along with the Omicron BA.1 and BA.2 subvariants by 131-, 61- and 49-fold respectively. Investigators predicted the vaccine’s efficacy against the original SARS-CoV-2 strain at 95%.

“The receptor-binding domain (RBD)- and spike (S) protein-binding IgG antibodies after booster immunization with UB-612 produced high cross-reactivity against multiple SARS-CoV-2 variants, including Alpha, Beta, Delta, Gamma and Omicron, similar to those of approved vaccines and boosters,” Palm said.

UB-612 contains a subunit RBD protein of the spike protein linked to a single chain fragment region of a human IgG1. It also includes five synthetic peptides with epitopes derived from S2, M and N proteins designed to promote B-cell and CD8+ T-cell memory responses. The vaccine includes an aluminum phosphate adjuvant.

“Unlike the first generation COVID-19 vaccines that are based on mRNA, adenovirus, or subunit platforms, UB-612 has an innovative manufacturing platform based on the combination of a subunit protein and a synthetic protein,” Palm said. “This unique combination allowed us to expand the antigenic composition of UB-612 to several other structural proteins in addition to the Spike, which is expected to provide protection through both T- and B-cell immune responses.

“The antigenic composition of UB-612 is designed to restore the protective level of the pre-existing immune responses stimulated by the primary immunization with COVID-9 vaccines. Unlike the existing vaccines, UB-612 recalls only the B-cells specific to the RBD, the key antigenic determinant responsible for stimulation of more than 90% of all SARS-CoV-2 neutralizing antibodies.”

Further research will determine whether UB-612 may offer a more long-lasting response as a booster to authorized vaccines. Immunity has been shown to wane quickly after vaccination with authorized vaccines.

“The most striking finding in the clinical trials was the induction of long-lasting virus- neutralizing antibodies, with the half-life estimated to be over 180 days after the second immunization,” Palm said.

UB-612 can be stored for 24 months at 35 to 46 degrees Fahrenheit, making it easier to transport and store than some vaccines, which could potentially improve vaccine accessibility to make low- and middle-income countries.

The phase 3 study is co-sponsored by the Coalition for Epidemic Preparedness Innovations (CEPI) with up to $9.25 million in funding.