Bivalent mRNA-1273.214 vaccine safe, immunogenic in children

Interim results from the ongoing Study 306, a phase III open-label trial, show improved immunogenicity and safety of the bivalent Omicron-containing mRNA-1273.214 vaccine in children 6 months to 5 years of age, both as a primary series and a booster.

The mRNA-1273.214 bivalent vaccine contains equal amounts of the spike messenger ribonucleic acids (mRNAs) of the ancestral Wuhan-Hu-1 strain and the Omicron B.1.1.529 (BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

“The mRNA-1273.214 vaccine demonstrated reactogenicity and safety comparable to the original mRNA-1273 vaccine,” reported study author Dr Avika Dixit, Director, Clinical Development Infectious Diseases at Moderna Therapeutics, at ESPID 2023. “This formulation containing a variant was more immunogenic than the original vaccine against the variant. This suggests that updating the vaccine to include a variant may lead to increase vaccine effectiveness in children.”

Study 306 was a two-part rollover (ROVER) study from Study 204 (KidCOVE) study, which was the basis for the approval of mRNA-1273 as a primary vaccine series in children, Dixit told ESPID delegates.

Children aged 6 months to 5 years who received a placebo in Study 204 or were not originally included in Study 204 but had not received any COVID-19 vaccines, received mRNA-1273.214 vaccine (25 μg) as a two-dose primary series, administered 28 days apart in part 1 of Study 306. [ESPID 2023, abstract O0026]

Children who received the original mRNA-1273 vaccine as a primary series in Study 204 received a bivalent booster series (10 μg) in part 2 of Study 306.

In both parts, blood samples were collected after dosing for immunogenicity analysis. Study 204 was used as a historical comparator. “Baseline characteristics were comparable between Study 204 and Study 306, except that there was a higher proportion of prior infections in Study 306,” said Dixit. “This reflected the increased seropositivity at the time of Study 306 enrolment.”

Part 1: mRNA-1273.214 as a primary vaccine

At the data cut-off date (Day 57), 179 participants had received at least one dose of mRNA-1273.214 primary series. Rates of local reactions at the injection site (pain, erythema, swelling, axillary swelling or tenderness) were generally comparable to, or slightly better than the original vaccine. Most events were grade 1 or 2.  No grade 4 events were reported.

Systemic reactions among children 6–36 months old (fever, irritability/crying, sleepiness, loss of appetite) and among children 37 months to 5 years of age (fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills) were comparable to the original primary series.

No grade 4 events were reported with bivalent mRNA-1273.214. Adverse events reported within 28 days after either dose were consistent with common childhood illnesses, with upper respiratory tract infections (URTIs) as the most common events (8.9 percent). “One child with a prior history of asthma experienced an exacerbation that was deemed a serious adverse event (AE) 14 days after the first dose, but it was not related to the study vaccine,” said Dixit.

There were no AEs of special interest, deaths, or AEs leading to discontinuation.

In terms of immunogenicity, neutralizing antibodies (NAbs) against Omicron BA.1 met the superiority criterion.

“Superiority of the BA.1-containing vaccine was demonstrated if the lower bound of the confidence interval for the geometric mean ratio (GMR) was >1,” said Dixit. “Regardless of the evidence of prior infection at baseline, post-vaccination titres rose substantially after vaccination with the bivalent mRNA-1273.214 primary series, resulting in a GMR of 25.4.”

The GMR against the ancestral strain also met the protocol-defined criteria for success based on noninferiority, she added.

Part 2: mRNA-1273.214 as a booster

In part 2 of Study 306, 539 participants had received the bivalent mRNA-1273.214 as a booster. Local reactions at the injection site were comparable to, or slightly better than the second dose of the original vaccine. The same trend was seen for systemic reactions for children 6 to 36 months old and for children 37 months to 5 years old.

“There were no grade 4 events with the bivalent booster. Adverse events reported within 28 days after the booster were also consistent with common childhood illnesses. Again, URTI was the most reported event,” reported Dixit.

One child experienced erythema multiforme two days after the booster, which resolved with treatment after a week. There were no severe AEs, deaths, or AEs leading to discontinuation.

NAbs against Omicron BA.1 met the superiority criterion. Among participants without evidence of prior infection, titres were substantially higher after the booster with a GMR of 12.5.

“The other co-primary objectives based on GMR against the ancestral strain and seroresponse rate against both the BA.1 subvariant and the ancestral strain were also met,” said Dixit.

Again, these data show that updating vaccine formulations to include variants may increase vaccine effectiveness against COVID-19 in children.

Moving forward

Dixit said Moderna continually updates their vaccines as SARS-CoV-2 evolves and public health needs change. “Variant-containing vaccines are intended to broaden cross-protective immunity while retaining protection against the ancestral strain,” she added.