Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan

• DOI: 10.1016/j.vaccine.2023.10.021
• Publication Date: 2023-10-13T20:29:36Z
• Authors: Takeshi Arashiro; Yuzo Arima; Jin Kuramochi; Hirokazu Muraoka; Akihiro Sato; Kumi Chubachi; Kunihiro Oba; Atsushi Yanai; Hiroko Arioka; Yuki Uehara; Genei Ihara; Yasuyuki Kato; Naoki Yanagisawa; Yoshito Nagura; Hideki Yanai; Akihiro Ueda; Akira Numata; Hideaki Kato; Hideaki Oka; Yusuke Nishida; Koji Ishii; Takao Ooki; Yuki Nidaira; Takahiro Asami; Torahiko Jinta; Akira Nakamura; Daisuke Taniyama; Kei Yamamoto; Katsushi Tanaka; Kankuro Ueshima; Tetsuji Fuwa; Ashley Stucky; Tadaki Suzuki; Chris Smith; Martin Hibberd; Koya Ariyoshi; Motoi Suzuki
• Keywords: Biomedical Research; Japan; Case-Control Studies; Humans; COVID-19; mRNA Vaccines; 3. Good health

Repeated emergence of variants with immune escape capacity and waning immunity from vaccination are major concerns for COVID-19. We examined whether the surge in Omicron subvariant BA.5 cases was due to immune escape or waning immunity through vaccine effectiveness (VE) evaluation.A test-negative case-control study was conducted in 16 clinics/hospitals during the BA.1/BA.2-dominant and BA.5-dominant periods. VE against symptomatic infection was estimated after adjusting for age, sex, comorbidity, occupation, testing frequency, prior infection, close contact history, clinic/hospital, week, and preventive measures. Absolute VE (aVE) was calculated for 2/3/4 doses, compared to the unvaccinated. Relative VE (rVE) was calculated, comparing 3 vs 2 and 4 vs 3 doses.13,025 individuals were tested during the BA.1/BA.2-dominant and BA.5-dominant periods with similar baseline characteristics. For BA.1/BA.2, aVE was 52 % (95 %CI:34-66) 14 days-3 months post-dose 2, 42 % (29-52) > 6 months post-dose 2, 71 % (64-77) 14 days-3 months post-dose 3, and 68 % (52-79) 3-6 months post-dose 3. rVE was 49 % (38-57) 14 days-3 months post-dose 3 and 45 % (18-63) 3-6 months post-dose 3. For BA.5, aVE was 56 % (27-73) 3-6 months post-dose 2, 32 % (12-47) > 6 months post-dose 2, 70 % (61-78) 14 days-3 months post-dose 3, 59 % (48-68) 3-6 months post-dose 3, 50 % (29-64) > 6 months post-dose 3, and 74 % (61-83) ≥ 14 days post-dose 4. rVE was 56 % (45-65) 14 days-3 months post-dose 3, 39 % (27-48) 3-6 months post-dose 3, 25 % (-2-45) > 6 months post-dose 3, and 30 % (-6-54) ≥ 14 days post-dose 4.Booster doses initially provided high protection against BA.5 at a level similar to that against BA.1/BA.2. However, the protection seemed shorter-lasting against BA.5, which likely contributed to the surge. Furthermore, rVE post-dose 4 was low even among recent vaccinees. These results support the introduction of variant-containing vaccines and emphasize the need for vaccines with longer duration of protection.