Evolution of Anti-SARS-CoV-2 IgG Antibody and IgG Avidity Post Pfizer and Moderna mRNA Vaccinations

Messenger RNA (mRNA) based vaccines (Pfizer/BioNTech and Moderna) are highly effective at providing immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is uncertainty about the duration of immunity, evolution of IgG antibody levels and IgG avidity (an index of antibody-antigen binding strength), and differences in the immune responses between vaccines. Here we performed a prospective pilot study of 71 previously COVID-19 free subjects upon receiving both doses of either the Pfizer (n = 54) or Moderna (n = 17) mRNA vaccine. Anti-spike protein receptor binding domain (RBD) IgG antibodies were measured longitudinally using a qualitative finger stick MidaSpot rapid test at the point-of-care for initial screening and a quantitative dry blood spot-based pGOLD laboratory test over ~ four months post-vaccination. The average anti-RBD IgG antibody levels peaked at ~ two weeks after the second dose vaccine and declined thereafter, while antibody avidity increased, suggesting antibody maturation. Moderna vaccine recipients compared to Pfizer vaccine recipients exhibited higher side effect severity, higher peak anti-RBD IgG antibody levels, and higher avidity up to the 90 days period. Differences in antibody levels diminished at ~ 120 days post-vaccination, in line with the similar efficacy observed in the two vaccines. The MidaSpot rapid test detected 100% anti-SARS-CoV-2 RBD positivity for fully vaccinated subjects in both Pfizer and Moderna cohorts post full vaccination but turned negative greater than 90 days post-vaccination for 5.4% of subjects in the Pfizer cohort, whose quantitative anti-IgG were near the minimum levels of the group. Immune responses were found to vary greatly among vaccinees. Personalized longitudinal monitoring of antibodies could be necessary to assessing the immunity duration of vaccinated individuals.

[1]  Samuel M. Brown,et al.  Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years — United States, January–March 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[2]  M. Carroll,et al.  Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays , 2021, Nature Protocols.

[3]  Andrew L. Phillips,et al.  Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[4]  L. Du,et al.  SARS-CoV-2 spike protein: a key target for eliciting persistent neutralizing antibodies , 2021, Signal Transduction and Targeted Therapy.

[5]  Esteban Ortiz Prado,et al.  SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates , 2021, NPJ vaccines.

[6]  M. Nussenzweig,et al.  mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants , 2021, Nature.

[7]  Charles Y. Tan,et al.  BNT162b vaccines protect rhesus macaques from SARS-CoV-2 , 2021, Nature.

[8]  M. Nussenzweig,et al.  Evolution of antibody immunity to SARS-CoV-2 , 2021, Nature.

[9]  X. Xia Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design , 2021, Viruses.

[10]  G. Gao,et al.  Viral targets for vaccines against COVID-19 , 2020, Nature reviews. Immunology.

[11]  P. Dormitzer,et al.  BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans , 2020, medRxiv.

[12]  J. Montoya,et al.  Quantification of antibody avidities and accurate detection of SARS-CoV-2 antibodies in serum and saliva on plasmonic substrates , 2020, Nature Biomedical Engineering.

[13]  C. Cordon-Cardo,et al.  Robust neutralizing antibodies to SARS-CoV-2 infection persist for months , 2020, Science.

[14]  M. Dake,et al.  Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity , 2020, Immunity.

[15]  A. Iafrate,et al.  Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients , 2020, Science Immunology.

[16]  F. Krammer SARS-CoV-2 vaccines in development , 2020, Nature.

[17]  Rebecca J. Loomis,et al.  SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness , 2020, Nature.

[18]  M. Chen,et al.  A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction , 2020, Nature Biotechnology.

[19]  C. Rice,et al.  Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals , 2020, Nature.

[20]  A. Sette,et al.  The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients , 2020, Science Immunology.

[21]  Vineet D. Menachery,et al.  Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients , 2020, Cell Reports Medicine.

[22]  J. Nie,et al.  Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay , 2020, Nature Protocols.

[23]  C. Sheridan Convalescent serum lines up as first-choice treatment for coronavirus , 2020, Nature Biotechnology.

[24]  C. Taddei,et al.  Diagnostic accuracy of an automated chemiluminescent immunoassay for anti‐SARS‐CoV‐2 IgM and IgG antibodies: an Italian experience , 2020, Journal of medical virology.

[25]  Y. Yazdanpanah,et al.  Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease Patients , 2020, Emerging infectious diseases.

[26]  P. Vollmar,et al.  Virological assessment of hospitalized patients with COVID-2019 , 2020, Nature.

[27]  Philip L. Felgner,et al.  A serological assay to detect SARS-CoV-2 seroconversion in humans , 2020, medRxiv.

[28]  A. Walls,et al.  Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein , 2020, Cell.

[29]  Kwaku Poku Asante,et al.  Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy , 2019, Nature Communications.

[30]  F. Elgh,et al.  Urea dilution of serum for reproducible anti-HSV1 IgG avidity index , 2019, BMC Infectious Diseases.

[31]  J. Montoya,et al.  Plasmonic gold chips for the diagnosis of Toxoplasma gondii, CMV, and rubella infections using saliva with serum detection precision , 2019, European Journal of Clinical Microbiology & Infectious Diseases.

[32]  H. Dai,et al.  Diagnosis of Zika virus infection on a nanotechnology platform , 2017, Nature Medicine.

[33]  H. Dai,et al.  Multiplexed Anti-Toxoplasma IgG, IgM, and IgA Assay on Plasmonic Gold Chips: towards Making Mass Screening Possible with Dye Test Precision , 2016, Journal of Clinical Microbiology.

[34]  Bo Zhang,et al.  A plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes , 2014, Nature Medicine.

[35]  C. Pannuti,et al.  Use of an Immunoglobulin G Avidity Test To Discriminate between Primary and Secondary Dengue Virus Infections , 2004, Journal of Clinical Microbiology.

[36]  C. Galli,et al.  Precision and Accuracy of a Procedure for Detecting Recent Human Immunodeficiency Virus Infections by Calculating the Antibody Avidity Index by an Automated Immunoassay-Based Method , 2002, Journal of Clinical Microbiology.

[37]  M. Furione,et al.  Diagnosis and outcome of preconceptional and periconceptional primary human cytomegalovirus infections. , 2002, The Journal of infectious diseases.

[38]  A. Lucas,et al.  Avidity as a Determinant of the Protective Efficacy of Human Antibodies to Pneumococcal Capsular Polysaccharides , 1999, Infection and Immunity.

[39]  K. Hedman,et al.  Recent rubella virus infection indicated by a low avidity of specific IgG , 1988, Journal of Clinical Immunology.

[40]  M. Nussenzweig,et al.  Dopamine in germinal centers , 2017, Nature Immunology.

[41]  C. Maroto,et al.  Are IgG antibody avidity assays useful in the diagnosis of infectious diseases? A review. , 1996, Microbios.