Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis

Abstract

The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study (NCT04405076) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups (n = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned (P < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 (P < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing.

Immune Memory Response After a Booster Injection of mRNA-1273 for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

“…In preliminary results at 6 months after two doses of mRNA-1273, neutralizing antibody levels against the Delta variant decreased compared to 28 days after the second dose of mRNA-1273 in the primary series, and approximately one-half of participants had no detectable neutralizing antibodies against the Delta variant in a pseudovirus research grade assay. 23 At 2 weeks after a booster dose of 50 µg of mRNA-1273, neutralizing antibody levels to the Delta variant increased to a similar level as neutralizing antibody titers against wild-type D614G at one month after the second dose of mRNA-1273 in the primary series. 23 The GMFR (Day 29 post-booster compared to pre-booster) achieved by mRNA-1273 booster, measured by the Delta variant pseudovirus assay (18.97; 95% CI, 16.72, 21.53), points to the ability of the mRNA-1273 vaccine booster to enhance a breadth of neutralizing antibody responses, including against the highly transmissible Delta variant.…”

“…23 At 2 weeks after a booster dose of 50 µg of mRNA-1273, neutralizing antibody levels to the Delta variant increased to a similar level as neutralizing antibody titers against wild-type D614G at one month after the second dose of mRNA-1273 in the primary series. 23 The GMFR (Day 29 post-booster compared to pre-booster) achieved by mRNA-1273 booster, measured by the Delta variant pseudovirus assay (18.97; 95% CI, 16.72, 21.53), points to the ability of the mRNA-1273 vaccine booster to enhance a breadth of neutralizing antibody responses, including against the highly transmissible Delta variant. Just as booster mRNA-1273 stimulated nAb levels against the original strain (GMTs 1892.7 at OL-D29 compared to 125.7 at OL-D1 (Supplementary Table 4), a booster injection of mRNA-1273 was able to broaden and increase nAb levels against the Delta variant, highlighting the critical benefits of mRNA-1273 booster dose.…”

“…15,16 Although the overall impact of variants on vaccine efficacy remains to be determined, some of these variants have decreased susceptibilities to neutralizing antibodies induced by current vaccines. [17][18][19][20][21][22][23] Furthermore, in a small study, immunity against variants wanes in vaccinated individuals such that approximately one-half did not have detectable neutralizing antibodies to the Delta variant 6 months after vaccination with mRNA-1273. 23 Although mRNA vaccine effectiveness against severe disease and hospitalization due to SARS-CoV-2 has remained high, in a large observational study performed by the Mayo Clinic, the mRNA vaccines were less effective against SARS-CoV-2 infections at a time when the Delta variant was prevalent.…”

Effects of Age, Sex, Serostatus and Underlying Comorbidities on Humoral Response Post-SARS-CoV-2 Pfizer-BioNTech Vaccination – A Systematic Review

“…the third vaccine dose was found to be effective in further boosting antibody levels in elderly people [80], in solid organ transplant recipients [81], and in patients receiving maintenance hemodialysis or peritoneal dialysis [82]. The third dose was also effective in reinforcing immunity against VoC [83]. Irrespective of the demographical or clinical conditions that would blunt the anti-SARS-CoV-2 antibody response, the importance of monitoring humoral immunity seems almost unquestionable for prioritizing vaccine boosters, including new vaccines able to efficiently protect against current and potentially future SARS-CoV-2 drifted VoC.…”

Auricular Acupressure for Adverse Events Following Immunization Related To COVID-19 Vaccine Injection: Study Protocol for a Multicenter, Three-Arm, Blinded Randomized Controlled Trial

“…Researches showed that novel coronavirus-19 vaccines (NCV) were of considerable e cacy, and improvement on e cacy, especially long-term protection, and exploration of new species of vaccines are being conducted [4][5][6][7][8]. Some new variants of COVID-19 have been emerging, which may exacerbate COVID-19 symptoms, while researches reveal that many still with good immunogenicity [9,10]. However, some studies show concern on prevention e cacy in the situation [11,12].…”