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

tetano

Editor, Senior Moderator
Vaccine


. 2023 Oct 13:S0264-410X(23)01194-5.
doi: 10.1016/j.vaccine.2023.10.021. Online ahead of print. Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan

Takeshi Arashiro[SUP] 1 [/SUP], Yuzo Arima[SUP] 2 [/SUP], Jin Kuramochi[SUP] 3 [/SUP], Hirokazu Muraoka[SUP] 4 [/SUP], Akihiro Sato[SUP] 5 [/SUP], Kumi Chubachi[SUP] 6 [/SUP], Kunihiro Oba[SUP] 7 [/SUP], Atsushi Yanai[SUP] 8 [/SUP], Hiroko Arioka[SUP] 8 [/SUP], Yuki Uehara[SUP] 9 [/SUP], Genei Ihara[SUP] 10 [/SUP], Yasuyuki Kato[SUP] 11 [/SUP], Naoki Yanagisawa[SUP] 12 [/SUP], Yoshito Nagura[SUP] 13 [/SUP], Hideki Yanai[SUP] 14 [/SUP], Akihiro Ueda[SUP] 15 [/SUP], Akira Numata[SUP] 16 [/SUP], Hideaki Kato[SUP] 17 [/SUP], Hideaki Oka[SUP] 18 [/SUP], Yusuke Nishida[SUP] 18 [/SUP], Koji Ishii[SUP] 19 [/SUP], Takao Ooki[SUP] 19 [/SUP], Yuki Nidaira[SUP] 20 [/SUP], Takahiro Asami[SUP] 21 [/SUP], Torahiko Jinta[SUP] 22 [/SUP], Akira Nakamura[SUP] 23 [/SUP], Daisuke Taniyama[SUP] 24 [/SUP], Kei Yamamoto[SUP] 18 [/SUP], Katsushi Tanaka[SUP] 17 [/SUP], Kankuro Ueshima[SUP] 25 [/SUP], Tetsuji Fuwa[SUP] 25 [/SUP], Ashley Stucky[SUP] 2 [/SUP], Tadaki Suzuki[SUP] 26 [/SUP], Chris Smith[SUP] 27 [/SUP], Martin Hibberd[SUP] 28 [/SUP], Koya Ariyoshi[SUP] 29 [/SUP], Motoi Suzuki[SUP] 2 [/SUP]



Affiliations
Abstract

Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.

Keywords: Coronavirus disease 2019 (COVID-19); SARS-CoV-2 variants; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Test-negative design; Vaccine effectiveness.

 
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