Serological assessment of the durability of vaccine-mediated protection against SARS-CoV-2 infection

ABSTRACT

Virus-neutralizing antibodies are often accepted as a correlate of protection against infection, though questions remain about which components of the immune response protect against SARS-CoV-2 infection. In this small observational study, we longitudinally measured spike receptor binding domain (RBD)-specific and nucleocapsid (NP)-specific serum IgG in a human cohort immunized with the Pfizer BNT162b2 vaccine. NP is not encoded in the vaccine, so an NP-specific response is serological evidence of natural infection. A greater than fourfold increase in NP-specific antibodies was used as the serological marker of infection. Using the RBD-specific IgG titers prior to seroconversion for NP, we calculated a protective threshold for RBD-specific IgG. On average, the RBD-specific IgG response wanes below the protective threshold 169 days following vaccination. Many participants without a history of a positive test result for SARS-CoV-2 infection seroconverted for NP-specific IgG. As a group, participants who seroconverted for NP-specific IgG had significantly higher levels of RBD-specific IgG following NP-seroconversion. RBD-specific IgG titers may serve as one correlate of protection against SARS-CoV-2 infection. These titers wane below the proposed protective threshold approximately six months following immunization. Based on serological evidence of infection, the frequency of breakthrough infections and consequently the level of SARS-CoV-2-specific immunity in the population may be higher than what is predicted based on the frequency of documented infections.

KEYWORDS:

• SARS-CoV-2
• vaccine
• antibody response
• waning immunity
• breakthrough infection

Acknowledgments

We gratefully acknowledge Drs. Ritesh Tandon and Stephen Stray for helpful discussions and the UMMC Department of Pathology and the UMMC Biobank for assistance with sample collection.

Author contributions

JTB, STL, and GDM conceived and designed the study. APF, MAB, KBS, DRE, DDM, and GCB performed the experiments. JTB, STL, GDM, and ATP analyzed the data. JTB wrote the first draft of the manuscript. All authors co-edited the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by The Robert M. Hearin Foundation, The Bower Foundation, and James L. Barksdale. JTB received support through the UMMC Molecular Center for Health and Disease [P20GM144041].