Phase 2/3 trial of new omicron-targeted vaccine shows efficacy in adolescents

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Most people have some immunity to SARS-CoV-2, whether from vaccination, previous infection, or both. A recent study published in The Lancet aimed to evaluate the safety and immunogenicity of an omicron-targeted COVID-19 vaccine, mRNA-1273.222, specifically in adolescents who had never been vaccinated but had tested positive for the virus. These findings revealed that a single dose of mRNA-1273.222 was effective in these unvaccinated, SARS-CoV-2-positive adolescents, demonstrating successful immunobridging to the two-dose mRNA-1273 primary series used in young adults.

Between December 21, 2022, and June 5, 2023, 379 adolescents, 378 tested positive for SARS-CoV-2, received at least one dose of mRNA-1273.222 and were included in the safety analysis. The reactogenicity profile was favorable compared to the mRNA-1273 primary series, with no new safety concerns identified. Unsolicited adverse events were reported in 49 participants (13%), but no deaths or events that led to study withdrawal.

“Data from a nationwide blood donor seroprevalence survey in the USA, based on about 143 000 blood donors, 16 and older, estimated that the overall SARS-CoV-2 seroprevalence rate due to vaccination or infection was 98.9% between October and December 2023; the corresponding SARS-CoV-2 seroprevalence rates were about 98.9% in adolescents aged 12–17 years and about 94.6% among children aged 0–11 years in December, 2022,” according to the investigators.

Part 3 of the phase 2/3 TeenCOVE trial was an open-label, single-arm study conducted in the USA and the Dominican Republic. It involved healthy, unvaccinated adolescents aged 12 to 17, who received two doses of 50 μg mRNA-1273.222 spaced six months apart. The primary outcomes focused on safety and reactogenicity, including the monitoring of solicited local and systemic adverse reactions within seven days post-vaccination, as well as unsolicited and prespecified adverse events throughout the study.

“The emergence of omicron subvariants containing more than 30 mutations in the SARS-CoV-2 spike protein28 has led to the need for variant-updated vaccines. In light of the continued genetic evolution of the SARS-CoV-2 virus, as well as the risks and complications associated with COVID-19 infection, our data highlight the ability of a variant-containing vaccine to provide potent, updated immune responses with a single dose in participants regardless of previous COVID-19 vaccination status, including those not previously vaccinated,” according to the investigators.

The immunogenicity analysis involved 245 SARS-CoV-2-positive adolescents and 296 SARS-CoV-2-negative young adults. A single dose of mRNA-1273.222 produced superior neutralizing antibody responses against the omicron subvariants BA.4 and BA.5, with a geometric mean ratio (GMR) of 48.95 (95% CI 44.21–54.21). Additionally, it generated non-inferior responses against the ancestral SARS-CoV-2 strain, with a GMR of 4.25 (95% CI 3.69–4.88) when compared to the mRNA-1273 primary series in SARS-CoV-2-negative young adults.

“Overall, a single dose of the variant-containing vaccine was well tolerated, with overall lower reactogenicity (any solicited reaction: 60·6%) than the original mRNA-1273 primary series (97·1%),” according to investigators.

The primary immunogenicity outcome was assessed by comparing neutralizing antibody responses 28 days after the first dose of mRNA-1273.222 in SARS-CoV-2-positive adolescents with responses measured 28 days after the second dose of a 100 μg primary series of mRNA-1273 in SARS-CoV-2-negative 18-25 old young adults from the COVE trial.

Limitations of this study include its open-label design, which may introduce bias, and the lack of data on live virus neutralizing antibodies and cellular immune responses. The follow-up period for participants was relatively short. Additionally, the comparator group was primarily composed of White non-Hispanic young adults, while the study participants were mostly Hispanic or Latino adolescents, potentially affecting generalizability. The timing of enrollment for the comparator group coincided with the circulation of the original SARS-CoV-2 strain, which may have resulted in different immunity profiles. The study did not evaluate the influence of breakthrough infections on immunogenicity at day 29 or assess immunogenicity against more recent variants. Lastly, the report did not examine long-term antibody persistence following single-dose vaccination.

The benefits observed with mRNA-1273.222 in this study are likely to extend to future variant-containing vaccines. Continuous monitoring of neutralization and vaccine effectiveness against emerging variants is essential for shaping future COVID-19 vaccination strategies. These findings support the implementation of a simplified single-dose vaccination schedule with variant-containing mRNA vaccines, regardless of individuals' prior vaccination history.

Reference:

Safety and immunogenicity of a single-dose omicron-containing COVID-19 vaccination in adolescents: an open-label, single-arm, phase 2/3 trial. Lancet. September 25, 2024. Accessed September 30, 2024. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00501-2/fulltext

This article was initially published by our sister publication, Contagion.