1 Omicron BA.1, BA.

2 and COVID-19 booster vaccination

2 Suvichada Assawakosri1,2, Sitthichai Kanokudom1,2, Nungruthai Suntronwong1, Jiratchaya

3 Puenpa1, Thaneeya Duangchinda3, Warangkana Chantima4,5, Pattarakul Pakchotanon3, Juthathip
4 Mongkolsapaya6,7, Nasamon Wanlapakorn1, Sittisak Honsawek2, Yong Poovorawan1,8

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5

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6 Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University,
7 Bangkok, 10330, Thailand

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8 Department of Biochemistry, Osteoarthritis and Musculoskeleton Research Unit, Faculty of
9 Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross

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10 Society, Bangkok, 10330, Thailand
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11 Molecular Biology of Dengue and Flaviviruses Research Team, National Center for Genetic
12 N
Engineering and Biotechnology, National Science and Development Agency, NSTDA, Pathum
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13 Thani 12120, Thailand
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14 Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine, Siriraj Hospital,
15 Mahidol University, Bangkok 10700, Thailand
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16 Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of

17 Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
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18 Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of
19 Oxford, Oxford, OX3 7BN, UK
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20 Chinese Academy of Medical Science(CAMS) Oxford Institute (COI), University of Oxford,
21 Oxford, U.K.
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22 FRS(T), the Royal Society of Thailand, Sanam Sueapa, Dusit, Bangkok 10330, Thailand.
23 *Corresponding Author
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24 Prof. Yong Poovorawan (Yong.P@chula.ac.th)

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 1 To The Editor- In reply to the correspondence from Tjan et al. [1] regarding the

2 heterologous booster in healthy adults previously immunized with two doses of CoronaVac [2],

3 the additional knowledge on immunogenicity of the booster (3rd dose) with BNT162b2 in

4 BNT162b2-primed individuals against the BA.2 Omicron variant will help promote the vaccine

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5 uptake and coverage in the midst of a surge in BA.2 Omicron worldwide.

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6 As of February 2022, the Omicron variant was further classified into four main sub-

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7 lineages, including BA.1, BA.1.1, BA.2, and BA.3. Moreover, an epidemiological surveillance

8 on COVID-19 showed that BA.2 sub-lineages become the dominant variant globally [3]. In

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9 Thailand, the BA.2 sub-lineages has been detected since the end of January 2022. The proportion

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of BA.2 sub-lineages rapidly increased and accounted for more than 90% of positive cases
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11 reported in March, 2022 [4]. Potent serum neutralizing antibody (NAbs) against BA.1 was
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12 observed after the heterologous booster in individuals previously immunized with 2 doses of

13 CoronaVac [2]. Considering the waning immunity after primary series vaccination and the high
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14 transmissibility and potential immune escape of BA.2 sub-lineage, we further determined the
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15 immunogenicity of the mRNA-1273 booster against BA.1 and BA.2 in AZD1222-primed

16 individuals using the Focus reduction neutralization test (FRNT50) as previously described [2].
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17 Participants were 30 healthy Thai adults aged 18 years old and above (mean age 50.66
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18 years, SD 12.95) who completed two doses of AZD1222 vaccination and had no previous or

19 current COVID-19 infection. The participants received mRNA-1273 as a booster (3rd dose)
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20 vaccine at 5-7 months after the second dose of AZD1222. Blood samples were collected at 28

21 days after the booster. In accordance with the results previously reported by Tjan, et al. and Yu J,

22 et al. [1,5] The undetectable (titer<20) NAbs against both BA.1 and BA.2 were observed among

23 most of participants before the booster. At 28 days after the booster, the GMT of NAbs

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 1 significantly increased from 16.6 (95%CI: 13.2, 21.0) and 11.0 (95%CI: 9.6, 12.6) to 548

2 (95%CI: 415, 723) and 324 (95%CI: 214, 492) against BA.1 and BA.2, respectively. The results

3 demonstrated that after the mRNA booster, the NAbs titers against BA.2 was slightly lower than

4 those against BA.1 (Figure 1).

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5 These preliminary results indicate that the heterologous booster with mRNA vaccine in

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6 AZD1222-primed individuals could induce a robust antibody response that can cross-neutralize

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7 both BA.1 and BA.2 omicron variants.

8 Footnotes

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Conflicts of Interest: The authors declare no conflict of interest.
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10 Acknowledgments: We would like to thank the staff of the Center of Excellence in Clinical
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11 Virology and all the participants for helping and supporting this project. We also thank the

12 Ministry of Public Health, Chulabhorn Royal Academy, and Zullig pharma for providing the
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13 vaccines for this study.

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14 Funding Statement: This work was supported by the Health Systems Research Institute (HSRI),
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15 National Research Council of Thailand (NRCT), the Center of Excellence in Clinical Virology,

16 Chulalongkorn University, and King Chulalongkorn Memorial Hospital and was partially
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17 supported by the Second Century Fund (C2F), Chulalongkorn University. Thaneeya

18 Duangchinda was supported by National Center for Genetic Engineering and Biotechnology
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19 (BIOTEC Platform No. P2051613 to T.D.).

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 1 References

2 1. Lidya Handayani Tjan, Koichi Furukawa, Yukiya Kurahashi, et al. As well as

3 Omicron BA.1, high neutralizing activity against Omicron BA.2 can be induced by

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4 COVID-19 mRNA booster vaccination. J Infect Dis. 2022.

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5 2. Assawakosri S, Kanokudom S, Suntronwong N, et al. Neutralizing Activities against

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6 the Omicron Variant after a Heterologous Booster in Healthy Adults Receiving Two

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7 Doses of CoronaVac Vaccination. J Infect Dis. 2022. doi:10.1093/infdis/jiac092

8 3. COVID-19 Weekly Epidemiological Update Edition: World Health Organization

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9 (WHO). [cited 2022 8 April]. 86:[Available from:

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https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-
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11 19---5-april-2022.
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12 4. Puenpa J, Rattanakomol P, Saengdao N, et al. Molecular characterisation and tracking

13 of the severe acute respiratory syndrome coronavirus 2, Thailand, 2020–2022.

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14 Research square [Preprint: not peer reviewed]. Posted online 12 April 2022. doi:
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15 10.21203/rs.3.rs-1545056/v1
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16 5. Yu J, Collier A-RY, Rowe M, et al. Neutralization of the SARS-CoV-2 Omicron

17 BA.1 and BA.2 Variants. N Engl J Med. 2022; 386:1579-1580.

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1 Figure legend

2 Figure 1. Neutralizing antibody titers of SARS-CoV-2 against BA.1 (purple) and BA.2 (blue)

3 omicron variants at pre-booster and 28 days post-booster. Neutralization of SARS-CoV-2 was

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4 measured using the focus reduction neutralization test (FRNT50). Each data point represents an

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5 individual who received mRNA-1273 as a booster dose. Error bars indicate GMT and 95%

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6 confidence interval (CI). Values below the limit of detection (titer<20) were substituted with a

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7 titer of 10.

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