Background: mRNA COVID-19 vaccines are playing a key role in controlling the COVID-19 pandemic. The relationship between post-vaccination symptoms and strength of antibody responses is unclear. Objective: To determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. Design: Single center, prospective, observational cohort study. Setting: Participants worked at Walter Reed National Military Medical Center and were seen monthly at the Naval Medical Research Center Clinical Trials Center. Participants: Generally healthy adults that were not severely immunocompromised, had no history of COVID-19, and were seronegative for SARS-CoV-2 spike protein prior to vaccination. Measures: Severity of vaccine-associated symptoms was obtained through participant completed questionnaires. Testing for IgG antibodies against SARS-CoV-2 spike protein and receptor binding domain was conducted using microsphere-based multiplex immunoassays. Results: 206 participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers one month after vaccination. We also observed that 1) post-vaccination symptoms were inversely correlated with age and weight and more common in women, 2) systemic symptoms were more frequent after the second vaccination, 3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and 4) older age was associated with lower titers. Limitations: Study only observes antibody responses and consists of healthy participants. Conclusions: Lack of post-vaccination symptoms following receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies one month after vaccination
The lack of correlati on betw een vaccine -associated symptoms and a ntibody ti te rs has two importan t implications for mRNA S ARS-CoV-2 vaccines. First, in dividuals tha t exhi bit few symptoms after vaccination can be r eassure d tha t this do es not mean the vaccine “didn’t work .” Indeed, in this cohor t individuals with few to no symptoms were just as likely to have develop ed str ong antibody resp onses as individuals that exhibi ted subs tanti al symptoms. Second , the immunological p at hways responsible for mRNA vaccine-induced AEs may not be r equired for d evelopmen t of robust antib ody responses. mRNA vaccines induce inflammatio n thr ough multiple pa thways, including ligatio n of innate immune recep tors, r eleas e of inflammatory cytok ines and chemokines, a nd activati on of antigen pres enting cells, natur al killer cells, and a ntigen-specific T and B cells (26-31). The exact pathways each mRNA vaccine induces, however, lik ely varies depen din g on factors such as the consti tuen ts of t he lipid nanopa rticl e, the cellula r upt ake pathways for th e lipid nanopar ticle, t he amoun t of contamina ting double-str anded RNA, nucle otid e modifications, a nd the a ntigen being enco ded by the d elivere d mRNA. Given th e lack of association b etwee n symptoms and anti body tite rs, we specula te th at some pa th ways may be expen dable for d evelopmen t of robust a daptive immune r esponses. If such path ways can be defined, then effor ts on developing mRN A vaccines that minimally activa te such pa thways could be advantageo us.