Neutralizing antibodies against the SARS-CoV-2 Omicron variant following two CoronaVac vaccinations and a Pfizer/BioNTech mRNA vaccine booster

Sao Paulo, May 15^th, 2022

Dear Editor

In a previous study conducted by our group, we evaluated 41 subjects who were vaccinated with two doses of the CoronaVac SARS-CoV-2 vaccine, with an interval of 28 days between doses, and subsequently received a booster of the mRNA vaccine from Pfizer/BioNTech¹. We determined the neutralizing capacity against the SARS CoV-2 Omicron variant 62.7 days following the administration of the booster.

In this investigation, we extended our initial findings on the same study subjects by reporting levels of neutralizing antibodies against the Omicron variant at a mean of 151.5 days after the booster vaccine.

Neutralizing antibodies against Omicron decreased in the subjects, since the first result showed a 85.3% positivity, whereas at day 151.5 (p = 0.0336), this percentage fell to 60.5%. The virus neutralization titer (VNT) also decreased at day 151.5 post-booster as opposed to day 62.7 VNT (p = 0.0256).

There is very limited knowledge about the activity and duration of neutralizing antibodies in vaccinated people after a two-dose vaccine schedule with an inactivated vaccine (CoronaVac) followed by a booster dose with an mRNA vaccine, as currently recommended by the Brazilian Ministry of Health²-⁴. To the best of our knowledge, this is the first report of anti-Omicron neutralizing antibodies in sera following a protracted period (day 151.5) post-mRNA vaccine booster. Our parallel findings from other studies suggest that vaccine effectiveness wanes over time following a booster vaccination⁵,⁶. In one study conducted during the Omicron variant outbreak in our country, vaccine effectiveness against COVID-19-associated hospitalization was 91% versus 78% among those who received the third dose of mRNA vaccine in periods equal to or less than two months in comparison with periods of more than four months after the second dose of vaccine, respectively⁶.

The post-vaccination sera with virus neutralization activity and the virus neutralization titer (VNT) against the SARS-CoV-2 Omicron variant at two different time frames are shown in Table 1. This prospective study recruited 41 subjects who have never been infected with SARS-CoV-2 and were vaccinated with two doses of the CoronaVac (Sinovac Life Sciences, Beijing, China) SARS-CoV-2 vaccine. Thirty-eight of these individuals received a booster immunization with the Pfizer mRNA vaccine. The vaccination protocol, immunization dates and quantification of neutralizing antibodies against the Omicron variant using the Cytopathic Effect-based Virus Neutralization Test had been previously reported⁵. Most subjects (90.2%) were female and their ages ranged from 30 to 77 years old with a median of 54 years. The majority (65.9%) were <60 years old. The presence of virus neutralization activity was defined as the absence of cytopathic activity at a serum dilution ≥ 1:20. The statistical analysis was performed by means of the Fisher’s exact test and the paired Wilcoxon test.

Table 1
Neutralizing antibody activity against the Omicron SARS-CoV-2 variant in sera from subjects who received two doses of the CoronaVac vaccine followed by a Pfizer mRNA vaccine booster.

Mean days post-booster	Nº tested	Nº with neutralizing activity (%)	Median VNT (IQR)
62.7	34	29 (85.3%)a	1: 40 (0, 1: 320)b
151.5	38	23 (60.5%)	1: 20 (0, 1: 160)

• The presence of virus neutralization activity was defined as the absence of cytopathic activity at a serum dilution > 1:20. VNT, virus neutralization titer; IQR, interquartile range); ^ap = 0.0336; ^bp = 0.0256

It should be noted that measurement of the in vitro VNT is not the only determinant of the level of protection against SARS-CoV-2. Anamnestic humoral and cell-mediated immune responses against a new infection also influence viral persistence and disease severity.

Despite this limitation, we believe that the findings of our study contribute to a better understanding of the effectiveness of the current Brazilian SARS-CoV-2 vaccination schedule, as it supports the current Brazilian guideline, which recommends a booster dose of a Covid-19 mRNA vaccine for the general population after completion of the primary vaccination series².

We conclude that this vaccination schedule provides limited protection against the Omicron SARS-CoV-2 variant as it wanes significantly over five months. Our findings of decreased immunity over time also suggest that a second booster dose may be beneficial and should be recommended for specific populations².

ACKNOWLEDGMENTS

We wish to thank all participants from Instituto de Medicina Tropical de São Paulo from whom the pre and post-immunization sera were collected. We thank the many colleagues and staff from LIM-52 (Virology Laboratory), at Instituto de Medicina Tropical de São Paulo who participated in all phases of the study.

REFERENCES

• ¹
  Silva Jr AR, Villas-Boas LS, Tozetto-Mendoza TR, Honorato L, Paula A, Witkin SS, et al. Generation of neutralizing antibodies against Omicron, Gamma and Delta SARS-CoV-2 variants following CoronaVac vaccination. Rev Inst Med Trop Sao Paulo. 2022;64:e19.
• ²
  Brasil. Ministério da Saúde. Gabinete do Ministro. Nota técnica nº 59/2021-SECOVID/GAB/SECOVID/MS. Administração de dose de reforço de vacinas contra a Covid-19 em pessoas com mais de18 anos. [cited 2022 May 16]. Available from: https://www.gov.br/saude/pt-br/coronavirus/vacinas/plano-nacional-de-operacionalizacao-da-vacina-contra-a-covid-19/notas-tecnicas/2021/nota-tecnica-no-592021-secovid-gab-secovid-ms.pdf/view
  » https://www.gov.br/saude/pt-br/coronavirus/vacinas/plano-nacional-de-operacionalizacao-da-vacina-contra-a-covid-19/notas-tecnicas/2021/nota-tecnica-no-592021-secovid-gab-secovid-ms.pdf/view
• ³
  Kanokudom S, Assawakosri S, Suntronwong N, Auphimai C, Nilyanimit P, Vichaiwattana P, et al. Safety and Immunogenicity of the third booster dose with inactivated, viral vector, and mRNA COVID-19 vaccines in fully immunized healthy adults with inactivated vaccine. Vaccines (Basel). 2022;10:86.
• ⁴
  Yorsaeng R, Suntronwong N, Phowatthanasathian H, Assawakosri S, Kanokudom S, Thongmee T, et al. Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults. Vaccine. 2022;40:524-30.
• ⁵
  Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Amir O, Freedman L, et al. Protection by a fourth dose of BNT162b2 against Omicron in Israel. N Engl J Med. 2022;386:1712-20.
• ⁶
  Ferdinands JM, Rao S, Dixon BE, Mitchell PK, DeSilva MB, Irving SA, et al. Waning 2-dose and 3-dose effectiveness of mRNA vaccines against COVID-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance: VISION Network, 10 states, August 2021-January 2022. MMWR Morb Mortal Wkly Rep. 2022;71:255-63.

• ETHICS
  This study was approved by the Brazilian National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa – CONEP), registration Nº 30419620.1.0000.0068. All subjects signed written informed consents.

• FUNDING : MCMC receives a scholarship from CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico for the purpose of conducting scientific research, process Nº 309492/2018-1.

Publication Dates

• Publication in this collection
  17 June 2022
• Date of issue
  2022

History

• Received
  15 May 2022
• Accepted
  16 May 2022