Key Points Question Are neutralizing antibodies against the Omicron variant of SARS-CoV-2 sufficiently induced after 2 to 3 doses of the BNT162b2 messenger RNA vaccine in recipients of different ages? Findings In this cohort study of 82 Japanese participants, 28% and 6% had neutralizing antibodies against the Omicron variant at 2 and 7 months, respectively, after 2 doses of the vaccine; both titer values were low in all age groups. After receiving a booster vaccination, all participants acquired much higher levels of neutralizing antibodies irrespective of age. Meaning This study suggests that booster vaccination was associated with induction of higher levels of neutralizing antibodies against the Omicron variant, irrespective of the recipient’s age.

The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n = 23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Intriguingly, after the second vaccination, the neutralizing antibody titers of subjects against SARS-CoV-2 variants, including Omicron, all became seropositive, and significant fold-increases (21.1–52.0) were seen regardless of the disease severity of subjects. Our findings thus demonstrate that two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.

Continuous appearance of SARS-CoV-2 variants and mass vaccination have been intricately influencing on the COVID-19 situation. To elucidate the current status in Japan, we analyzed totally 2,000 sera in August (n = 1,000) and December (n = 1,000) 2021 collected from individuals who underwent a health check-up. The anti-N seropositive rate were 2.1% and 3.9% in August and December 2021, respectively, demonstrating a Delta variant endemic during that time; it was approximately twofold higher than the rate based on the PCR-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. These analyses revealed that effective immunity against the Delta variant was established in December 2021, however, prompt three-dose vaccination is needed to overcome Omicron’s outbreak.

BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues in public health. To control VOCs, it is important to know which COVID-19 convalescent sera have cross-neutralizing activity against VOCs and how long the sera maintain this protective activity.MethodsSera of patients infected with SARS-CoV-2 from March 2020 to January 2021 and admitted to Hyogo Prefectural Kakogawa Medical Center were selected. Blood was drawn from patients at 1-3, 3-6, and 6-8 months post onset. Then, a virus neutralization assay against SARS-CoV-2 variants (D614G mutation as conventional strain; B.1.1.7, P.1, and B.1.351 as VOCs) was performed using authentic viruses.ResultsWe assessed 97 sera from 42 patients. Sera from 28 patients showed neutralizing activity that was sustained for 3-8 months post onset. The neutralizing antibody titer against D614G significantly decreased in sera of 6-8 months post onset compared to those of 1-3 months post onset. However, the neutralizing antibody titers against the three VOCs were not significantly different among 1-3, 3-6, and 6-8 months post onset.DiscussionOur results indicate that neutralizing antibodies that recognize the common epitope for several variants may be maintained for a long time, while neutralizing antibodies having specific epitopes for a variant, produced in large quantities immediately after infection, may decrease quite rapidly.

Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages.