1887
Research Open Access
Like 0

Abstract

Background

To cope with the persistence of the COVID-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially for the primary vaccination course, and the heterologous Vaxzevria/Comirnaty regimen had shown better efficacy and immunogenicity than the homologous Comirnaty/Comirnaty regimen.

Aim

We wanted to determine if this benefit was retained after a third dose of an mRNA vaccine.

Methods

We combined an observational epidemiological study of SARS-CoV-2 infections among vaccinated healthcare workers at the University Hospital of Lyon, France, with a prospective cohort study to analyse immunological parameters before and after the third mRNA vaccine dose.

Results

Following the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens (adjusted hazard ratio (HR) = 1.88; 95% confidence interval (CI): 1.18–3.00; p = 0.008), but this was no longer the case after the third dose (adjusted HR = 0.86; 95% CI: 0.72–1.02; p = 0.082). Receptor-binding domain-specific IgG levels and serum neutralisation capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group.

Conclusion

The advantage conferred by heterologous vaccination was lost after the third dose in terms of both protection and immunogenicity. Immunological measurements 1 month after vaccination suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2023.28.15.2200746
2023-04-13
2024-10-15
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2023.28.15.2200746
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/28/15/eurosurv-28-15-2.html?itemId=/content/10.2807/1560-7917.ES.2023.28.15.2200746&mimeType=html&fmt=ahah

References

  1. Schmidt T, Klemis V, Schub D, Mihm J, Hielscher F, Marx S, et al. Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination. Nat Med. 2021;27(9):1530-5.  https://doi.org/10.1038/s41591-021-01464-w  PMID: 34312554 
  2. Pozzetto B, Legros V, Djebali S, Barateau V, Guibert N, Villard M, et al. Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination. Nature. 2021;600(7890):701-6.  https://doi.org/10.1038/s41586-021-04120-y  PMID: 34673755 
  3. Liu X, Shaw RH, Stuart ASV, Greenland M, Aley PK, Andrews NJ, et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet. 2021;398(10303):856-69.  https://doi.org/10.1016/S0140-6736(21)01694-9  PMID: 34370971 
  4. Klemis V, Schmidt T, Schub D, Mihm J, Marx S, Abu-Omar A, et al. Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens. Nat Commun. 2022;13(1):4710.  https://doi.org/10.1038/s41467-022-32321-0  PMID: 35953492 
  5. Hillus D, Schwarz T, Tober-Lau P, Vanshylla K, Hastor H, Thibeault C, et al. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. Lancet Respir Med. 2021;9(11):1255-65.  https://doi.org/10.1016/S2213-2600(21)00357-X  PMID: 34391547 
  6. Niyomnaitham S, Quan Toh Z, Wongprompitak P, Jansarikit L, Srisutthisamphan K, Sapsutthipas S, et al. Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac, ChAdox1 nCov-19 and BNT162b2 plus BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adults. Hum Vaccin Immunother. 2022;18(6):2091865.  https://doi.org/10.1080/21645515.2022.2091865  PMID: 35816053 
  7. Mayr FB, Talisa VB, Shaikh O, Yende S, Butt AA. Effectiveness of homologous or heterologous Covid-19 boosters in veterans. N Engl J Med. 2022;386(14):1375-7.  https://doi.org/10.1056/NEJMc2200415  PMID: 35139265 
  8. Andersson NW, Thiesson EM, Laursen MV, Mogensen SH, Kjær J, Hviid A. Safety of heterologous primary and booster schedules with ChAdOx1-S and BNT162b2 or mRNA-1273 vaccines: nationwide cohort study. BMJ. 2022;378:e070483.  https://doi.org/10.1136/bmj-2022-070483  PMID: 35831006 
  9. Lustig Y, Gonen T, Meltzer L, Gilboa M, Indenbaum V, Cohen C, et al. Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose. Nat Immunol. 2022;23(6):940-6.  https://doi.org/10.1038/s41590-022-01212-3  PMID: 35534723 
  10. Au WY, Cheung PPH. Effectiveness of heterologous and homologous covid-19 vaccine regimens: living systematic review with network meta-analysis. BMJ. 2022;377:e069989.  https://doi.org/10.1136/bmj-2022-069989  PMID: 35640925 
  11. Liu X, Munro APS, Feng S, Janani L, Aley PK, Babbage G, et al. Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial. J Infect. 2022;84(6):795-813.  https://doi.org/10.1016/j.jinf.2022.04.018  PMID: 35405168 
  12. Bal A, Simon B, Destras G, Chalvignac R, Semanas Q, Oblette A, et al. Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation in France. Nat Commun. 2022;13(1):6316.  https://doi.org/10.1038/s41467-022-33910-9  PMID: 36274062 
  13. Saade C, Gonzalez C, Bal A, Valette M, Saker K, Lina B, et al. Live virus neutralization testing in convalescent patients and subjects vaccinated against 19A, 20B, 20I/501Y.V1 and 20H/501Y.V2 isolates of SARS-CoV-2. Emerg Microbes Infect. 2021;10(1):1499-502.  https://doi.org/10.1080/22221751.2021.1945423  PMID: 34176436 
  14. Lee HK, Go J, Sung H, Kim SW, Walter M, Knabl L, et al. Heterologous ChAdOx1-BNT162b2 vaccination in Korean cohort induces robust immune and antibody responses that includes Omicron. iScience. 2022;25(6):104473.  https://doi.org/10.1016/j.isci.2022.104473  PMID: 35637788 
  15. Accorsi EK, Britton A, Shang N, Fleming-Dutra KE, Link-Gelles R, Smith ZR, et al. Effectiveness of Homologous and Heterologous Covid-19 Boosters against Omicron. N Engl J Med. 2022;386(25):2433-5.  https://doi.org/10.1056/NEJMc2203165  PMID: 35613039 
  16. Behrens GMN, Barros-Martins J, Cossmann A, Ramos GM, Stankov MV, Odak I, et al. BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19. Nat Commun. 2022;13(1):4872.  https://doi.org/10.1038/s41467-022-32527-2  PMID: 35982040 
  17. Regev-Yochay G, Gonen T, Gilboa M, Mandelboim M, Indenbaum V, Amit S, et al. Efficacy of a fourth dose of Covid-19 mRNA vaccine against Omicron. N Engl J Med. 2022;386(14):1377-80.  https://doi.org/10.1056/NEJMc2202542  PMID: 35297591 
  18. Vanhems P, Barrat A, Cattuto C, Pinton JF, Khanafer N, Régis C, et al. Estimating potential infection transmission routes in hospital wards using wearable proximity sensors. PLoS One. 2013;8(9):e73970.  https://doi.org/10.1371/journal.pone.0073970  PMID: 24040129 
  19. Voirin N, Payet C, Barrat A, Cattuto C, Khanafer N, Régis C, et al. Combining high-resolution contact data with virological data to investigate influenza transmission in a tertiary care hospital. Infect Control Hosp Epidemiol. 2015;36(3):254-60.  https://doi.org/10.1017/ice.2014.53  PMID: 25695165 
  20. Payne RP, Longet S, Austin JA, Skelly DT, Dejnirattisai W, Adele S, et al. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Cell. 2021;184(23):5699-5714.e11.  https://doi.org/10.1016/j.cell.2021.10.011  PMID: 34735795 
/content/10.2807/1560-7917.ES.2023.28.15.2200746
Loading

Data & Media loading...

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error