The vaccine candidate has potential, but needs further modification to produce greater immune responses

Vaccination 3_AS

In a phase-one, dose-ranging trial, a novel lipid nanoparticle (LNP)-encapsulated self-amplifying RNA (saRNA) vaccine candidate against COVID-19 was found to be safe and immunogenic at low-dose levels, but was not successful in inducing 100% seroconversion. The findings, published in eClinicalMedicine, warrant further modification of the vaccine to produce more consistent and robust humoral responses.

The saRNA platform has previously demonstrated promising results in preclinical models. This is the first human trial to investigate the safety and immunogenicity of a COVID-19 vaccine based on the platform.

Study details

In the phase-one trial, conducted at Imperial Clinical Research Facility and other participating centres in London, 192 healthy participants aged 18–45 years were intramuscularly administered two injections of LNP-nCoVsaRNA vaccine 4 weeks apart, across six dose levels in the range of 0.1μg to 10.0μg.

No unexpected short-term safety signals were seen following two doses of the vaccine. The vaccine was well tolerated without any serious adverse events related to vaccination. The reactogenicity increased with increasing dose, with the highest frequency of grade three reactions being seen in individuals receiving the 10.0μg dose. Common systemic reactions reported were fatigue, headache, myalgia, arthralgia, chills, and nausea.

In terms of binding antibody responses, the seroconversion at week 6 remained suboptimal, the highest rates being 61% (at the 10.0μg dose) as measured by enzyme-linked immunosorbent assay and 87% (at the 5.0μg and 10.0μg doses) as measured by immunoblot. The highest anti-spike immunoglobin antibody titre was seen with the 5.0μg dose, with no further augmentation in individuals receiving the 10.0μg dose.

Although immune responses were observed at low-dose (1.0μg) and ultralow-dose (0.1μg) levels, the proportion of participants producing neutralising antibodies at week 6 remained low (33% and 15%, respectively). Neutralising antibodies were detected at week 6 in 48% and 43% of participants in the 5.0μg group and the 10.0μg group respectively.

Room for improvement

The authors concluded: ‘Global demand for COVID-19 vaccines will remain high in the coming decade, given the emergence of lethal severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2] escape-variants and expected requirement for booster vaccination. If modified to improve antibody titres, encapsulated saRNA could provide potential advantages for vaccine development, including scalability, tolerability, and flexibility in antigen design, to meet requirements for the ongoing response to the COVID-19 pandemic.’

This trial was co-funded by the Medical Research Council UKRI, the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth. Paul F McKay and Robin J Shattock are listed as co-inventors on a patent application for the SARS-CoV-2 saRNA vaccine. The remaining authors have no disclosures.

This article was originally published on Medscape, part of the Medscape Professional Network.

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