Anti-spike S1 IgA, anti-spike trimeric IgG, and anti-spike RBD IgG response after BNT162b2 COVID-19 mRNA vaccination in healthcare workers

IgG and IgA response after BNT162b2 mRNA vaccination

  • Gian Luca Salvagno Section of Clinical Biochemistry, University of Verona, Verona, Italy and Service of Laboratory Medicine, Pederzoli Hospital, Peschiera del Garda, Italy
  • Brandon Henry The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
  • Giovanni Di Piazza Medical Direction, Pederzoli Hospital, Peschiera del Garda, Italy
  • Laura Pighi Section of Clinical Biochemistry, University of Verona, Verona, Italy
  • Simone De Nitto Section of Clinical Biochemistry, University of Verona, Verona, Italy
  • Damiano Bragantini Infectious Diseases Unit, Pederzoli Hospital, Peschiera del Garda, Italy
  • Gianluca Gianfilippi Medical Direction, Pederzoli Hospital, Peschiera del Garda, Italy
  • Giuseppe Lippi Section of Clinical Biochemistry, University of Verona, Verona, Italy
Keywords: COVID-19, vaccination, immune response, antibodies, IgA


Background: Most studies on immune response after coronavirus disease 2019 (COVID-19) vaccination focused on serum IgG antibodies and cell-mediated immunity, discounting the role of anti-SARS-CoV-2 neutralizing IgA antibodies in preventing viral infection. This study was aimed to quantify serum IgG and IgA neutralizing antibodies after mRNA COVID-19 vaccination in baseline SARS-CoV-2 seronegative healthcare workers.

Methods: The study population consisted of 181 SARS-CoV-2 seronegative healthcare workers (median age 42 years, 59.7% women), receiving two doses of Pfizer COVID-19 vaccine BNT162b2. Serum samples were collected before receiving the first vaccine dose, 21 days (before the second vaccine dose) and 50 days afterwards. We then measured anti-spike trimeric IgG (Liaison XL, DiaSorin), anti-spike receptor binding domain (RBD) IgG (Access 2, Beckman Coulter) and anti-spike S1 subunit IgA (ELISA, Euroimmun). Results were presented as median and interquartile range (IQR).

Results: Vaccine administration elicited all anti-SARS-CoV-2 antibodies measured. Thirty days after the second vaccine dose, 100% positivization occurred for anti-spike trimeric IgG and anti-spike RBD IgG, whilst 1.7% subjects remained anti-spike S1 IgA negative. The overall increase of antibodies level over baseline after the second vaccine dose was 576.1 (IQR, 360.7-867.8) for anti-spike trimeric IgG, 1426.0 (IQR, 742.0-2698.6) for anti-spike RBD IgG, and 20.2 (IQR, 12.5-32.1) for anti-spike S1 IgA. Significant inverse association was found between age and overall increase of anti-spike trimeric IgG (r=-0.24; p=0.001) and anti-spike S1 IgA (r=-0.16; p=0.028), but not with anti-spike RBD IgG (r=-0.05; p=0.497).

Conclusions: mRNA COVID-19 vaccination elicits sustained serum levels serum anti-spike trimeric IgG and anti-spike RBD IgG, while also modestly but significantly increasing those of serum anti-spike S1 IgA.


1. Lippi G, Sanchis-Gomar F, Henry BM. Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Ann Transl Med 2020;8:497.
2. Delikhoon M, Guzman MI, Nabizadeh R, Norouzian Baghani A. Modes of Transmission of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) and Factors Influencing on the Airborne Transmission: A Review. Int J Environ Res Public Health 2021;18:395.
3. Lotfi M, Hamblin MR, Rezaei N. COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta. 2020 Sep;508:254-66.
4. Szkaradkiewicz-Karpińska AK, Szkaradkiewicz A. Towards a more effective strategy for COVID-19 prevention (Review). Exp Ther Med 2021;21:33.
5. World Health Organization. Vaccines and immunization: What is vaccination? Avaialble at: Last accessed, May 24, 2021.
6. Fauci, A.S. The story behind COVID-19 vaccines. Science 2021;372:109.
7. Wu Z, Li T. Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives. Pharm Res 2021;38:473-8.
8. Abdool Karim SS, de Oliveira T. New SARS-CoV-2 Variants - Clinical, Public Health, and Vaccine Implications. N Engl J Med 2021;384:1866-8.
9. Xiaojie S, Yu L, Lei Y, Guang Y, Min Q. Neutralizing antibodies targeting SARS-CoV-2 spike protein. Stem Cell Res. 2020 Dec 15;50:102125. doi: 10.1016/j.scr.2020.102125. Epub ahead of print.
10. Russell MW, Moldoveanu Z, Ogra PL, Mestecky J. Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection. Front Immunol 2020 Nov 30;11:611337.
11. Wang Z, Schmidt F, Weisblum Y, Muecksch F, Barnes CO, Finkin S, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 2021;592:616-22.
12. Ketas TJ, Chaturbhuj D, Cruz-Portillo VM, Francomano E, Golden E, Chandrasekhar S, et al. Antibody responses to SARS-CoV-2 mRNA vaccines are detectable in saliva. bioRxiv [Preprint]. 2021 Mar 11:2021.03.11.434841. doi: 10.1101/2021.03.11.434841.
13. Danese E, Montagnana M, Salvagno GL, Peserico D, Pighi L, De Nitto S, et al. Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series. Clin Chem Lab Med. 2021 Apr 12. doi: 10.1515/cclm-2021-0339. Epub ahead of print.
14. McDonald I, Murray SM, Reynolds CJ, Altmann DM, Boyton RJ. Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2. NPJ Vaccines 2021;6:74.
15. The Lancet Infectious Diseases. The rocky road to universal COVID-19 vaccination. Lancet Infect Dis. 2021 May 14:S1473-3099(21)00275-9. doi: 10.1016/S1473-3099(21)00275-9. Epub ahead of print.
16. Borchering RK, Viboud C, Howerton E, Smith CP, Truelove S, Runge MCet al. Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios - United States, April-September 2021. MMWR Morb Mortal Wkly Rep 2021;70:719-24.
17. Butler SE, Crowley AR, Natarajan H, Xu S, Weiner JA, Bobak CA, et al. Distinct Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals. Front Immunol 2021;11:618685.
18. Lippi G, Sciacovelli L, Trenti T, Plebani M. Kinetics and biological characteristics of humoral response developing after SARS-CoV-2 infection: implications for vaccination. Clin Chem Lab Med. 2021 Jan 21. doi: 10.1515/cclm-2021-0038. Epub ahead of print.
19. Ejemel M, Li Q, Hou S, Schiller ZA, Tree JA, Wallace A, et al. A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction. Nat Commun 2020;11:4198.
20. Lippi G, Mattiuzzi C. Clinical value of anti-SARS-COV-2 serum IgA titration in patients with COVID-19. J Med Virol 2021;93:1210-1.
21. Sterlin D, Mathian A, Miyara M, Mohr A, Anna F, Claër L, et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med 2021;13:eabd2223.
22. Pisanic N, Randad PR, Kruczynski K, Manabe YC, Thomas DL, Pekosz A, et al. COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva. J Clin Microbiol 2020;59:e02204-20.
23. Isho B, Abe KT, Zuo M, Jamal AJ, Rathod B, Wang JH, et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol 2020;5:eabe5511.
24. Varnaitė R, García M, Glans H, Maleki KT, Sandberg JT, Tynell J, et al. Expansion of SARS-CoV-2-Specific Antibody-Secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients. J Immunol 2020;205:2437-46.
25. Quinti I, Mortari EP, Fernandez Salinas A, Milito C, Carsetti R. IgA Antibodies and IgA Deficiency in SARS-CoV-2 Infection. Front Cell Infect Microbiol 2021;11:655896.
26. Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, et al. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med 2021;384:1412-23.
27. Saad-Roy CM, Morris SE, Metcalf CJE, Mina MJ, Baker RE, Farrar J, et al. Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes. Science 2021;372:363-70.
Original paper