By Marie Rosenthal, MS
A novel intranasal, live-attenuated COVID-19 vaccine candidate appears to induce both humoral and cellular immunity in healthy, previously unvaccinated adults, according to data being presented at IDWeek 2023, being held in Boston, Oct. 11-15 (abstract 1938).
“The data we will be presenting on Friday summarizes the immune response that we have observed in our first in-human clinical trial that we have conducted with CoviLiv,” said Johanna Kaufmann, PhD, the executive vice president for oncology and immunology at Codagenix, during a media briefing, sponsored by IDWeek 2023.
The live-attenuated viral vaccine contains replication-competent, whole live SARS-CoV-2 Wuhan strain that is synthetically engineered using “Codagenix’s synthetic attenuated viral engineering platform to convert this virus from a pathogen to a safe vaccine virus,” Dr. Kaufmann explained.
The double-blind, placebo-controlled, dose-escalation study randomly assigned healthy adults to either the live-attenuated vaccine, delivered intranasally, or a placebo group. The participants were healthy adults who had never received a COVID-19 vaccine. This poster discussed results for six of the intervention group who received multiple doses of vaccine.
The researchers obtained sera on days 1, 29 and 57, looking for humoral immune responses. In addition, they established T-cell responses on days 1 and 36.
Data being presented by Codagenix, the developer of CoviLiv, show that six participants who received two doses of 5×106 plaque-forming units of CoviLiv showed robust induction of both humoral and cellular immune responses. T-cell reactivity appears to be specific for multiple viral antigens beyond the frequently mutating spike protein of SARS-CoV-2, enabling induction of broad immunity to numerous viral antigens. This could increase its efficacy against variants, according to the company.
“Antibodies are the general immune response that are often reported for COVID vaccines, and we have seen regimen-dependent induction of spike-specific IgG [immunoglobulin G] or antibodies in serum,” Dr. Kaufmann said. “Those increases were mirrored when testing for the neutralizing capacity of these viruses.”
In addition to humoral immune response measures, “we then characterize the T-cell response—a cellular immune response—in a little bit more detail.
“Here we saw dose- and regimen-dependent increases of interferon gamma or T-cell responses after restimulation with the peptides that cover more than the spike protein of SARS-CoV-2.”
The secretion of several cytokines, including interferon gamma, tumor necrosis factor?alpha and interleukin-2, has been “reported to be relevant for protection occurring after natural infection,” she said.
“We saw a T-cell repertoire profile similar to infection as you would expect with a live-attenuated virus vaccine in 80% of the recipients of the high-dose cohort. While none of these conversions were observed after placebo, there are several measures of T-cell clonality or the breadth and diversity of the T-cell that do respond to vaccination. And several of these measures were increased.
“Importantly we saw, based on known mapping of T-cell receptor sequences, with antigen reactogenic not only to spike [protein] but other proteins of the viral particle, particularly nucleocapsid and glycoprotein. The data we will present on Friday show that CoviLiv can induce a robust systemic immune response after intranasal delivery of this life-attenuated virus vaccine,” Dr. Kaufman said.
However, CD8 T-cell responses were less pronounced with CoviLiv, which Dr. Kaufmann said surprised her, because they typically have a direct toxic ability against viruses. However, as they learn more about the body’s immune response to natural SARS-CoV-2 infection, they are finding that CD4 T-cell responses are critical.
“It is actually quite fascinating to see how well this attenuated virus mimics natural infection, which gives us high hope to contribute now in a more complex vaccination ecosystem that this virus can contribute to hybrid immunity,” Dr. Kaufmann said.
In a different phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults (ClinicalTrials.gov Identifier: NCT04619628 https://clinicaltrials.gov/study/NCT04619628), the vaccine was shown to be well tolerated with few side effects.
“We have observed a low frequency of mild immunogenicity events,” Dr. Kaufmann said, adding that “all of these were lower in frequency than in the placebo group who have also received intranasal administrations. In particular, cardinal symptoms like fever or loss of taste or smell that you might have been used to from natural COVID infection have not been observed at all with this vaccine.”
The live-attenuated vaccine might have some advantages over current mRNA vaccines, according to Dr. Kaufmann.
“Obviously, live-attenuated virus vaccines are a modality that have been around for decades,” she said, so they may be more appealing to people who are hesitant to receive a vaccine using the new mRNA technology. In addition, the nasal administration might appeal to people who are afraid of needles. The vaccine might also be able to address some of the inequities of COVID-19 vaccine administration, where rates are still low in some socioeconomically disadvantaged countries, because it should be less expensive to produce and distribute. Although the vaccine requires refrigeration, it does not have the cold-chain needs that mRNA vaccines have, she added.
Dr. Kaufmann was quick to point out that despite these positive results, the efficacy of the vaccine has not been proved in a large trial. However, CoviLiv is being evaluated for safety and efficacy in a global phase 3 study as part of the World Health Organization's Solidarity Trial Vaccines.
“Today's topic is particularly timely as we search for new vaccines and treatments to combat the evolving strains of COVID-19,” said Susan Bleasdale, MD, the medical director of infection prevention and control at UI Health, in Chicago.
In related news, Codagenix recently announced that the Biomedical Advanced Research and Development Authority has entered into a contract with Codagenix to support the costs of a phase 2b clinical study of CoviLiv for the prevention of symptomatic COVID-19 in people who have completed their primary authorized COVID-19 vaccine series and their last COVID-19 vaccine was at least three months before. The agreement is part of Project NextGen, an initiative by the Department of Health and Human Services to advance a pipeline of new, innovative vaccines and therapeutics for COVID-19. NextGen will provide an initial $10 million and up to $389 million to cover costs of a 10,000-person, phase 2b clinical study of CoviLiv to be evaluated against one of the authorized mRNA XBB.1.5 comparator vaccines in volunteers who have received prior COVID-19 vaccine trials.
CoviLiv is being jointly developed by Codagenix and the Serum Institute of India Pvt. Ltd.
