mRNA-1273

induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified

mRNA elicited potent pseudovirus neutralizing activity and S-specific binding antibodies production in mice; Efficient agains both the D614 type and the D614G mutant.

Although slightly declining (as expected), the vaccinated healthy adults in all age groups produced high titres of binding and neutralizing antibodies (targeted at SARS-CoV-2 Spike RBD) at day 119 post first immunization. The antibody titres were high enough to manifest potent live- and pseudovirus neutralization in vitro. No serious adverse effects were observed.

Some of the antibodies identified in the B cells from immunized volunteers which bound SARS-CoV-2 Spike S or BRD domain of the original SARS-CoV-2 were found to have a decreased or no neutralizing activity against some of the emerging Spike variants (E484K or N501Y or the K417N:E484K:N501Y combination). Overall, the plasma neutralizing activity against these variants was present but decreased.

At days 7 or 14 after a single-dose vaccination, the health-care workers with prior SARS-CoV-2 infection developed higher anti-Spike antibodies and more potent live virus neutralizing capacity compared to the non-infected subjects. Sample size: 13 with evidence of previous symptomatic SARS-CoV-2 infection + 10 with evidence of previous asymptomatic SARS-CoV-2 infection + 7 seronegative. Data were pooled with

The adverse reactions after vaccine administration were mostly mild or moderate and temporary. SARS-CoV-2-neutralizing antibodies were elicited in titres higher than those observed in sera of convalescent patients (with seroconversion in 28 days after the first dose in most of the subjects). Sample size: For immunogenicity analyses: ≥55 years of age: 94 (placebo subgroup) + 95 (50μg doses subgroup) + 94 (100 μg doses subgroup); 18–<55 years of age: 92 (placebo group) + 90 (50μg doses group) + 95 (100 μg doses group). For safety analyses: 100 subjects in each of the subgroups. Dosing: Two 50 μg or two 100 μg doses, 28 days apart. Primary outcomes: Safety, reactogenicity, and immunogenicity.

Although the capacity of sera of vaccinated subjects and convalescent individuals to neutralize SARS-CoV-2 B.1.1.7 variant Spike pseudovirus decreased, the decrease was only modest (2.1-fold and 1.5-fold, respectively); therefore, SARS-CoV-2 variant B.1.1.7 should not be of a major concern for mRNA-1273 recipients and convalescent individuals.

SARS-CoV-2 Spike protein of some strains, especially of B.1.351 (“South Africa”), seems to be several-fold more resistant to neutralization by antibodies from vaccinated subjects compared to the wild type virus. This is especially true for individuals with a single dose vaccination without prior SARS-CoV-2 infection or exposure. The sera of subjects vaccinated with two doses, or of those with previous virus exposure, seem to retain neutralizing capacity to some extent, however.

Sera of vaccinated subjects (14-days post second dose) displayed titres of SARS-CoV-2-neutralizing antibodies which should be protective against the infection; although, the neutralizing capacity against assayed emergent strains (e. g. B.1.1.7) was significantly weaker compared to an earlier variant (nCoV/USA_WA1/2020).

A pooled analysis with

(Data pooled with those for

COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

(Data pooled with

(Analyses pooled with

(Analyses pooled with

Although 3.8-fold decrease in neutralizing titres against B.1.351 compared to B.1 was observed in the sera of vaccinated individuals, the sera were still capable to neutralize the SARS-CoV-2 variant in vitro.

A single dose administration in most of the subjects who were seropositive prior to the vaccination elicited presumably sufficient immune reaction. Adverse reactions were more frequent in this cohort compared to infection-naïve subjects. Generally, adverse reactions were more frequent after the second dose administration. Sample size: 151 seronegative + 55 seropositive. Dosage: One or two doses.

Sera from vaccinated individuals displayed only a modest decrease in neutralization capacity against SARS-CoV-2 Spike-psudotyped virus corresponding to the B.1.429 strain (“California”). The magnitude of decrease of neutralization titres against B.1.351 strain, however, was of a greater concern.

209 days after the administration of the second vaccine dose, antibody activity remained high in all age groups (although the titres were lower in the higher-age groups). Based on the model used, the antibody binding activity half-life was 43 or 109 days, neutralizing antibody activity half-life against pseudovirus infection was 69 or 173 days, and neutralizing antibody activity half-life against live virus infection was 68 or 202 days. The model suggesting longer half-lives assumes that decay rates decrease over time. Sample size: 33 donors. Dosage: Two doses of 100 μg.

Vaccination elicited CD4+ T cell response which might effectively recognize some of the common SARS-CoV-2 variants.

Analysis pooled with

The sera of most of the vaccinated individuals retained some neutralization capacity against SARS-CoV-2 Omicron Spike-pseudotyped virus in vitro. The neutralization titres were severalfold lower, however. A comparatively smaller decrease in efficacy was observed in the case of three-dose regimen (in dialysis patients) or in convalescent patients who had received two doses of the vaccine. 

The sera of the majority of individuals who were previously vaccinated with Ad26.COV2.S and have recently received a booster dose of an mRNA vaccine were capable of Delta and Omicron variants’ (pseudoviruses’) neutralization in vitro. Administration of a third vaccine dose substantially increased neutralization of SARS-CoV-2 pseudovirus by sera of vaccinated individuals. A two-dose vaccination regimen did not provide a high level of protection against newly emerging variants, especially Omicron. The neutralization was generally less potent against the Delta variant and even less potent against the Omicron variant, compared to the wild type. Previous infection mostly increased neutralization even in individuals without a booster. The antibody protection decreased with time past from the vaccination. Sample size: 24 (recent vaccination) + 23 (distant vaccination) + 8 (convalescent and distant vaccination) + 33 (with a booster). Main outcome: 2 or 3 doses.

The mRNA vaccination induced an immune response in most of the CAR T cell therapy (targeting B cell antigens) recipients. Spike-specific antibody levels were dependent on patients’ circulating B cell counts, but CD4 T cell responses were noted even in some patients with severe B cell depletion. Sample size: 6 + 1 healthy control. Dosage: 2-dose regimen. 

Compared to an ancestral strain, the neutralization of SARS-CoV-2 Omicron variants BA.1, BA.1.1, or BA.2 by sera of vaccinated individuals was detectable, yet s weaker. 

mRNA1273 vaccine-elicited serum was more effective against B.1. as against the variants Kappa, Delta or Epsilon. 

No neutralization of Omicron was observed in subjects vaccinated with two doses 6 months after the second immunization, but the third booster dose of BNT16b2 neutralized Omicron. Three months after booster dose, the neutralization weakened.