mRNA-1273 vaccine response non-inferior to young adults in children from 6 months

10th November 2022

The mRNA-1273 vaccine has been shown to generate an antibody response in children from 6 months that is non-inferior to young adults

The mRNA-1273 vaccine directed against COVID-19 has been shown to produce an antibody response in children aged from 6 months to 5 years that was comparable to the response elicited by young adults, aged 18 to 25 according to the findings of a study by US researchers.

It has become recognised that the efficient transmission of COVID-19 from school-age children and adolescents to household members can occur and lead to the hospitalisation of adults with secondary cases of the virus. While both COVID-19 infections and deaths are less frequent in children compared to adults it has been estimated that of 4.1 million COVID-19 deaths, 0.4% (16,100) occurred in those under 20 years of age and of which, 47% were in those age 0 to 9 years. Vaccination against COVID-19 is known to be effective at reducing hospitalisation and death in adults and the mRNA-1273 vaccine is also known to be safe and effective at inducing an immune response and preventing COVID-19 in children 6 to 11 years of age. However, whether the vaccine remains safe and able to elicit a satisfactory antibody response in children from 6 months of age is uncertain and was the purpose of the present study.

The US researchers undertook a phase 2 – 3 trial to determine the most appropriate dose in younger children. This revealed that a 25-μg dose of the mRNA-1273 vaccine was safe in children from 6 months of age. The team then randomised children aged 6 months to 23 months and between 2 and 5 years in a 3:1 ratio to two 25-μg doses administered 28 days apart or matching placebo. The aim of the study was to assess whether the antibody response was non-inferior to that generated by those aged 18 to 25.

mRNA-1273 vaccine antibody response in children from 6 months

A total of 1761 children with a median age of 16 months (51.7% male) received two doses of the vaccine and of whom, 89.4% tested negative for COVID-19. The median duration of follow-up was 68 days.

When assessed at day 57, the neutralising antibody geometric mean concentration was 1781 (95% CI 1272 – 1563) among those aged 6 – 23 months. This compared to a mean concentration of 1391 in those aged 18 to 25 (who had received 2 x 100 μg doses) and met the pre-defined criteria for non-inferiority. A similar and non-inferior response was also generated in those aged 2 – 5 years. In addition, there were no major safety concerns with adverse events mainly low-grade and transient.

In terms of vaccine effectiveness, within the 6 – 23-month group, infection occurred in 3.4% of the mRNA-1273 vaccine group and 6.6% of the placebo group, giving a vaccine efficacy of 50.6% (95% CI 21.4 – 68.6%). Among those aged 2 to 5, the vaccine efficacy was 36.85 (95% CI 12.5 – 54%) during the period of time when Omicron was the predominately circulating variant.

The authors concluded that two 25-μg doses of the vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults.

Citation
Anderson EJ et al. Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age. N Eng J Med 2022

Antibody response from Omicron BA.4/BA.5 bivalent booster similar to original vaccine

31st October 2022

The antibody response to an Omicron BA.4/BA.5 bivalent booster appears to be similar to that generated after a fourth monovalent mRNA vaccine

The antibody response generated after receipt of an Omicron BA.4/BA.5 bivalent booster appears no better than the response induced after a fourth dose of monovalent mRNA vaccine dose against COVID-19 variants according to a small pre-print study by a team of US researchers.

The evolving nature of the COVID-19 virus had led to many variants such as Omicron. However, this variant too has further mutated to create the sublineages BA.2.12.1, BA.4 and BA.5 that which can escape neutralisation by current vaccines. As a result, companies have quickly adapted their vaccines and the FDA has given emergency use authorisation to what have been termed ‘bivalent boosters’ produced by both Moderna and Pfizer-BioNTech. Similarly, the European Medicines Agency, has also recommended authorising an adapted bivalent vaccine targeting the Omicron sub-variants BA.4 and BA.5.  The bivalent vaccines contain two messenger RNA components of COVID-19; one directed at the original strain and the other towards the BA.4 and BA.5 lineages of the omicron variant. There is currently limited data on the antibody response generated with these bivalent vaccines. However, one recent study compared the Moderna bivalent vaccine as a second booster to receiving a fourth dose of the original, monovalent vaccine. The results showed that the bivalent vaccine elicited a higher neutralising antibody response against omicron BA.4 and BA.5 than the monovalent vaccine. Moreover, preliminary data on a bivalent vaccine manufactured by Pfizer BioNTech, was reported to show that in sera collected from participants 7 days after administration of a 30-µg booster dose of the Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine, there was a substantial increase in the Omicron BA.4/BA.5 neutralising antibody response above pre-booster levels.

In the present study, researchers collected sera from individuals who had previously received three doses of a monovalent vaccine, followed by a single dose of a bivalent vaccine. The researchers then compared the neutralising capacity against COVID-19 to panels of sera collected from participants who had received either 3 or 4 monovalent mRNA vaccine doses as well as from individuals who experienced a breakthrough infection with BA.4/BA.5. The sera samples were all tested against the original COVID-19 strain, Omicron sublineages, BA.1, BA.2, BA.4/BA.5, BA.4.6, BA.2.75 and BA.2.75.2.

Antibody response for COVID-19 variants

A total of 74 patients provided samples of whom, 19 with a mean age of 55.3 years (89.5% female) had previously received four doses of a monovalent vaccine although those who were given a bivalent booster were younger (mean age 36.4, 76.2% female). Serum samples were collected a mean of 24 days following the booster dose for the monovalent group and after a similar interval (mean 26.4 days) in the bivalent group.

All the cohorts displayed a high antibody response to the original COVID-19 strain but there were no differences for the other variants. In other words, receiving a booster vaccine which targeted both the original COVID-19 strain and the BA.4/BA.5 variants, did not produce a superior antibody response against all of the variants tested, compared to boosting with a fourth dose of a monovalent vaccine.

The authors suggested that these results may indicate immunological imprinting, i.e., whereby initial exposure to one virus strain effectively primes B cell memory and limits the development of memory B cells and neutralising antibodies against new minor variant strains of the virus. Moreover, they suggested that follow-up studies were needed to determine if the antibody responses change over time.

Citation
Wang Q et al. Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot. BioRxiv 2022

Omicron BA.4/BA.5-adapted bivalent vaccine increases antibody response

19th October 2022

The Omicron BA.4/BA.5-adapted-bivalent COVID-19 vaccine demonstrated a substantial increase in antibody response above pre-booster levels

The Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine showed a substantial increase in neutralising antibody response according to a press release by the joint manufacturers Pfizer and BioNTech. The findings come from a Phase 2/3 clinical trial evaluating the safety, tolerability, and immunogenicity of the companies’ bivalent vaccine.

Unfortunately, the release does not provide much numerical data, instead reporting that a 30-µg booster dose of the Omicron BA.4/BA.5-adapted bivalent vaccine demonstrated a substantial increase in the antibody response above pre-booster levels based on sera taken 7 days after administration.

Furthermore, there were similar responses seen across individuals aged 18 to 55 years of age and those older than 55 years of age. In fact, when comparing the response among individuals older than 55 years of age who received either the bivalent vaccine, or the original vaccine, the booster dose of the original vaccine elicited more limited increase in the neutralising antibody response against the Omicron BA.4/BA.5 variants.

Taken together, the press release suggests that the results suggest that a 30-µg booster dose of the Omicron BA.4/BA.5-adapted bivalent vaccine is likely to provide better protection against the Omicron BA.4 and BA.5 variants than the original vaccine for both younger and older adults. Additionally, the Omicron BA.4 and BA.5-adapted bivalent vaccine was well tolerated with early data indicating a favourable safety profile, similar to that of the original vaccine.

In the study, sera were collected 7 days after the second booster dose from participants aged older than 55 (40 in each age group) and then compared to the 7-day post sera from 40 participants older than 55 years of age who had received three prior doses of the original BNT162b2 COVID-19 vaccine and a second booster with original vaccine.

Sera were also collected 7 days post second booster dose from participants 18 to 55 years of age who received the Omicron BA.4/BA.5-adapted bivalent booster (n=40) to compare bivalent vaccine responses in younger and older adults. The time between third and fourth doses for the bivalent vaccine recipients was approximately 11 months compared to approximately 6 months for the original vaccine.

Despite this difference, baseline neutralising antibody titers were generally similar across groups. Among the participants, samples were equally stratified at baseline in each group between those who either with or without a prior or current history of COVID-19.

The companies added that data measuring responses at one-month post-administration of the Omicron BA.4/BA.5 bivalent vaccine booster (rather than the currently reported 7 days) are expected in the coming weeks and will be used to support potential full licensure and global registration of the companies’ Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine.

It was also mentioned that the companies have initiated a similar Phase 1/2/3 trial investigating the Omicron BA.4/BA.5-adapted bivalent vaccine among children 6 months through 11 years of age.