Breaking: Novel Live-Attenuated Intranasal COVID-19 Vaccine Yields Significant Humoral, Cellular Immune Response

Two doses of an investigational live attenuated COVID-19 intranasal vaccine produced broad humoral and cellular immune responses in a first in-human trial, according to research presented during a late breaking oral abstract session¹ on Friday at IDWeek 2023.

The findings are based on data from the randomized, placebo-controlled phase 1 CDX-CoV-001 clinical trial (NCT04619628) of CoviLiv^TM, a novel vaccine candidate that is derived from SARS-CoV-2/Wuhan, engineered to genetically convert the virus from disease-causing pathogen to stable, safe live-attenuated vaccine.² The intent for the vaccine, according to a statement from CoviLiv developer Codagenix, Inc, is to "produce an immune response to the entire virus rather than the frequently mutating spike protein,"² an effect that could yield more robust immunity and conceivably broader protection against COVID-19 variants, the company said.²

The intranasal delivery route is meant to mimic natural infection and to induce a localized immune response in the nasal cavity, explained lead study author Johanna Kaufmann, PhD, executive vice president for oncology and immunology at Codagenix Inc, in a pre-IDWeek press briefing on Tuesday.³ There currently are no approved live attenuated or intranasal vaccines against COVID-19.

CDX-CoV-001 was a dose escalation study of CoviLiv used a primary vaccination series in healthy adults to establish the vaccine's safety and tolerability.¹

Data presented at the meeting highlighted the immune response to CoviLiv among participants in the study cohort that received the highest dose of 5x10⁶ pfu (n=6/group).

Investigators characterized humoral immune response on days 1, 29, and 57 and analyzed T-cell functionality on days 1 and 36.

RESULTS¹

On post-vaccination study day 57, after 2 doses of the intranasal vaccine, researchers reported a greater than 2-fold increase in spike-specific IgG among all participants, with a geometric mean fold rise of 19.5 (95% CI, 3.4 to 113.8).

Neutralizing antibodies at day 57 were induced 2.6-fold based on microneutralization assay and by 4.9-fold using pseudovirus neutralization assay(95% CI 1.0 to -7.0 and 1.4 to 16.6, respectively).

On post-vaccination day 36, after restimulation with a variety of SARS-CoV-2 peptides to mimic virus strains and variants, T-cell response increased by 2.5-fold in the study cohort receiving 1 dose and by nearly double that, 4.5-fold, in the 2-dose cohort, according to the study abstract. In contrast, researchers observed no increase in T-cell reactivity after restimulation with spike-only virus peptides, further highlighting T-cell response to multiple viral antigens beyond the spike protein^.1

“The study findings provide a glimpse into what could be the next generation of COVID-19 vaccines that provide differentiated protection to more people,” lead author Kaufmann said.² “Vaccine administration by nose and easier storage can increase access to vaccinations for underserved areas across the world.”²

CoviLiv does not require cold chain storage, according to Codagenix, which simplifies stockpiling in areas where refrigeration for vaccines is scarce.² Intranasal administration provides an alternative to intramuscular vaccination, another feature that could promote vaccine uptake in areas with lower vaccination rates.²

References

1. Kauffman JK, who, and who, et al. CoviLivtm, a novel intranasal live-attenuated COVID-19 vaccine candidate, induces robust humoral and cellular immunity in first-in-human clinical trial CDX-CoV-001. Abstract presented at IDWeek 2023; October 11-15, 2023; Boston, MA.
2. Study shows COVID-19 intranasal vaccine candidate produces robust immune response. News release. Codagenix Inc. October 11, 2023. Accessed October 11, 2023. https://codagenix.com/codagenix-announces-late-breaking-presentation-of-positive-clinical-immunogenicity-data-for-covid-19-vaccine-candidate-coviliv-at-idweek-2023/
3. Press conference.

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