Safety and immunogenicity of the Pfizer/BioNTech SARS-CoV-2 mRNA third booster vaccine dose against the BA.1 and BA.2 Omicron variants

• Published in: Med (New York, N.Y. : Online) Vol. 3; no. 6; pp. 406 - 421.e4
• Main Authors: Seki, Yohei, Yoshihara, Yasuo, Nojima, Kiyoko, Momose, Haruka, Fukushi, Shuetsu, Moriyama, Saya, Wagatsuma, Ayumi, Numata, Narumi, Sasaki, Kyohei, Kuzuoka, Tomoyo, Yato, Yoshiyuki, Takahashi, Yoshimasa, Maeda, Ken, Suzuki, Tadaki, Mizukami, Takuo, Hamaguchi, Isao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.06.2022
• Subjects: adverse event; Antibodies, Neutralizing; Antibodies, Viral; BA.1; BA.1.1; BA.2; BNT162 Vaccine - immunology; BNT162b2 mRNA vaccine; Clinical and Translational; COVID-19 - prevention & control; Cross Reactions; cytokine signature; Humans; Immunity, Humoral; Immunization, Secondary; Immunogenicity, Vaccine; Neutralization Tests; neutralizing antibody; Omicron; RNA, Messenger; SARS-CoV-2; SARS-CoV-2 - genetics; subvariant; variant of concern; BNT162b2 mRNA vaccine; subvariant; SARS-CoV-2; cytokine signature; Translation to humans; variant of concern; neutralizing antibody; adverse event; Omicron; BA.1; BA.1.1; BA.2
• ISSN: 2666-6340; 2666-6359; 2666-6340
• DOI: 10.1016/j.medj.2022.04.013

The Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in Japan in November 2021. This variant contains up to 36 mutations in the spike protein, the target of neutralizing antibodies, and can escape vaccine-induced immunity. A booster vaccination campaign began with healthcare workers and high-risk groups. The safety and immunogenicity of the three-dose vaccination against Omicron remain unknown. A total of 272 healthcare workers were initially evaluated for long-term vaccine safety and immunogenicity. We further established a vaccinee panel to evaluate the safety and immunogenicity against variants of concern (VOCs), including the Omicron variants, using a live virus microneutralization assay. Two-dose vaccination induced robust anti-spike antibodies and neutralization titers (NTs) against the ancestral strain WK-521, whereas NTs against VOCs were significantly lower. Within 93–247 days of the second vaccine dose, NTs against Omicron were completely abolished in up to 80% of individuals in the vaccinee panel. Booster dose induced a robust increase in anti-spike antibodies and NTs against the WK-521, Delta, and Omicron variants. There were no significant differences in the neutralization ability of sera from boosted individuals among the Omicron subvariants BA.1, BA.1.1, and BA.2. Boosting increased the breadth of humoral immunity and cross-reactivity with Omicron without changes in cytokine signatures and adverse event rate. The third vaccination dose is safe and increases neutralization against Omicron variants. This study was supported by grants from AMED (grants JP21fk0108104 and JP21mk0102146). [Display omitted] •Neutralization titers (NTs) against Omicron decreased after two-dose mRNA vaccination•Three-dose vaccination increased anti-spike antibody and NTs against Omicron variants•Immunogenicity against Omicron subvariants did not change after three-dose vaccination•The cytokine signature remained unchanged after three-dose vaccination The SARS-CoV-2 Omicron variant, later named BA.1, has emerged as a highly transmissible variant due to the 36 mutations in its spike protein, which is the target of neutralizing antibodies; it can therefore escape vaccine-induced immunity. The Omicron subvariant, BA.2, was recently identified and has rapidly become a major variant of concern in many countries, including Japan. This study found that anti-spike antibody levels and neutralization ability decreased gradually 6–9 months after the second vaccination. A third dose dramatically increased the response against multiple Omicron variants. These results show that a booster shot increases neutralization antibodies against SARS-CoV-2 variants. Seki et al. report that a three-dose Pfizer/BioNTech mRNA vaccination induced a robust increase in anti-spike antibodies and neutralization titers against the WK-521, Delta, and Omicron variants. Immunogenicity against Omicron subvariants, including BA.1, BA.1.1, and three different BA.2 subvariants did not change following the third vaccine dose.