The messenger RNA COVID-19 vaccines, Moderna and Pfizer-BioNTech, are often lumped together in discussions of the fight to control the novel coronavirus.

But differences exist, as demonstrated by a study recently published in JAMA. Belgian researchers report a significantly higher humoral immunogenicity of the SARS-CoV-2 mRNA-1273 vaccine (Moderna) compared with the BNT162b2 vaccine (Pfizer-BioNTech) in infected as well as uninfected participants and across age categories.

"The higher mRNA content in mRNA-1273 compared with BNT162b2 and the longer interval between priming and boosting for mRNA-12733(4 weeks vs. 3 weeks for BNT162b2) might explain this difference," the authors point out.

The study cites past studies linking neutralization level after SARS-CoV-2 vaccination and protection against COVID-19, noting, "As such, the height of the humoral response after vaccination, which correlates with neutralizing antibody titers, might be clinically relevant."

The study team adds, "The SARS-CoV-2 messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) have each shown more than 90% efficacy in preventing COVID-19 illness, but to our knowledge, humoral immune responses have not been compared directly."

To remedy that, researchers invited healthcare workers at a tertiary-care center (Ziekenhuis Oost-Limburg, Belgium) who were scheduled for vaccination with two doses of either mRNA-1273 or BNT162b2 to participate in the prospective cohort. Participants underwent serologic testing prior to vaccination, as well as 6 to 10 weeks after the second dose, which was between April 27 and May 20, 2021.

The study team measured total immunoglobulin levels to the receptor-binding domain of the SARS-CoV-2 spike protein with an antiÐSARS-CoV-2 S enzyme immunoassay (Elecsys, Roche Diagnostics International Ltd). Then, after vaccination, they quantified how many antibodies were found against the SARS-CoV-2 nucleocapsid protein.

For purposes of the study, previous infection was defined as antinucleocapsid positivity at any point, antispike positivity before vaccination, and/or a history of positive polymerase chain reaction results on nasopharyngeal swab.

Antibody levels were compared after the second dose of each vaccine for the entire cohort, including those previously infected versus uninfected; and by age group (<35, 35-55, and >55 years).

Overall, 688 healthcare workers received the mRNA-1273 shot (mean age 43.2 years; 76.7% women; 21.8% previously infected with SARS-CoV-2) and 959 received the BNT162b2 vaccine (mean age 44.7 years; 84.9% women; 13.2% previously infected).

The researchers report that they observed higher antibody titers in participants vaccinated with two doses of mRNA-1273 compared with those vaccinated with BNT162b2 (geometric mean titer [GMT], 3836 U/mL [95% CI, 3,586-4,104] vs. 1,444 U/mL [95% CI, 1,350-1,544]; P <.001).

They also note that previously infected participants had higher antibody titers (GMT, 9461 U/mL [95% CI, 8,494-10,539]) compared with previously uninfected participants (GMT, 1613 U/mL [95% CI, 1,539-1,690]) (P <.001), adding, "In both groups, those vaccinated with mRNA-1273 had higher antibody titers compared with those vaccinated with BNT162b2 (previously uninfected: GMT, 2881 U/mL [95% CI, 2,721-3,051] vs. 1,108 U/mL [95% CI, 1,049-1,170]; P <.001; previously infected: GMT, 10,708 U/mL [95% CI, 9,311-12,315] vs. 8,174 U/mL [95% CI, 6,923-9,649]; P = .01). The difference in antibody levels according to previous infection was higher than the difference between the two mRNA vaccines."

The study also reveals that antibody levels negatively correlated with age in previously uninfected participants (correlation coefficient, -0.22; P <.001), and were highest among those younger than age 35 years. Although, the authors add, "Across all age categories, previously uninfected participants vaccinated with mRNA-1273 had higher antibody titers compared with those vaccinated with BNT162b2 (P <.001 for all comparisons. The type of mRNA vaccine remained independently associated with the log-transformed antibody titer in a multiple linear regression."

The researchers note that limitations of their study include the lack of data on cellular immunity and on neutralizing antibodies, as well as the specific focus on healthcare workers. "Whether the observed difference in antibody level translates to a difference in the duration of protection, the protection against variants of concern, and the risk of transmission needs further investigation," they write. "Future research should also address the relevance for patients with reduced antibody response after vaccination."

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