mRNA vaccines against respiratory infections in children: What’s new?

Despite the striking mortality burden of respiratory syncytial virus (RSV), no active vaccines are currently available to prevent RSV in children, says Dr Sherlock Lai, medical director, Moderna Singapore, at SiPPAC 2023.

“Like RSV, human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common seasonal viruses that cause respiratory disease. There are no approved vaccines currently to treat or prevent hMPV and PIV3 infections in children,” he continued.

mRNA-1345 and mRNA-1653 vaccines
mRNA-1345 is an investigational RSV vaccine of a single mRNA sequence encoding for a stabilized prefusion F glycoprotein. mRNA-1653 is a combination investigational vaccine with two distinct mRNA sequences encoding the fusion (F) proteins of hMPV and PIV3. The vaccine is designed to protect against hMPV and PIV3 infections.

Two phase I trials assessed the safety and immunogenicity of mRNA-1345 and mRNA-1653 vaccines in seropositive children 12–59 months of age. In the mRNA-1345 trial, 46 children who had an RSV infection received mRNA-1345 vaccine (15 or 30 µg) or placebo. In the mRNA-1653 trial, 27 children who had an hMPV and PIV3 infection received mRNA-1653 (10 or 30 µg) or placebo.

Antibody levels increased in both mRNA-1345 and mRNA-1653 groups after 1 month vs placebo. Two additional injections of mRNA-1345 did not further increase antibody levels after 5 months, so was a second injection of mRNA-1653 after 3 months. However, antibody levels remained substantially higher in both groups than prior to first vaccination.

Overall, vaccination with mRNA-1345 or mRNA-1653 vaccines was safe and induced neutralizing antibody response, said Lai. “The results support the continued development of both vaccines in young children,” he added.

mRNA-1273.214 bivalent vaccine
Children are not spared from COVID-19 infection. Bivalent vaccination with mRNA-1273.214 is shown to be safe and immunogenic in children 6 months to 5 years, both as a primary series and a booster in the phase III Study 306 trial, reported Lai.

The mRNA-1273.214 bivalent vaccine contains equal amounts of the spike mRNAs of the ancestral strain and the Omicron (BA.1) variant. Study 306 was a two-part rollover (ROVER) study of Study 204 (KidCOVE) which was the basis for the approval of the original mRNA-1273 vaccine as a primary vaccine series in children.

mRNA-1273.214 as a primary vaccine
In part 1 of Study 306, 179 children had received two doses of mRNA-1273.214 primary series by Day 57. Rates of local reactions at the injection site were slightly better than the original vaccine. Most events were grade 1 or 2. 

Systemic reactions were comparable to the original vaccine.

“One child had asthma exacerbation 14 days after the first dose but was not related to the vaccine,” said Lai. “There were no AEs of special interest, deaths, or AEs leading to discontinuation.”

As for immunogenicity, neutralizing antibodies (nAbs) against Omicron BA.1 met the superiority criterion (the lower bound of the confidence interval for geometric mean ratio (GMR) was >1).

“Regardless of the evidence of prior infection at baseline, post-vaccination titres rose substantially after vaccination with the bivalent mRNA-1273.214 as a primary series, resulting in a GMR of 25.4,” said Lai. “The GMR against the ancestral strain also met the protocol-defined criteria for success based on noninferiority.”

mRNA-1273.214 as a booster
In part 2 of the study, 539 children received the bivalent mRNA-1273.214 as a booster. Local reactions at the injection site and systemic reactions (both in 6 to 36 months old and in 37 months to 5 years old) were similar to the original vaccine.

There were no severe AEs, deaths, or AEs leading to discontinuation, said Lai.

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

Overall, the BA.1 bivalent vaccine demonstrated reactogenicity and safety comparable to the original vaccine. “Updating vaccine formulations to include a variant may increase vaccine effectiveness against COVID-19 in children,” Lai concluded.