While mRNA vaccines are administrated worldwide in an effort to contain the COVID-19 pandemic, the heterogeneity of the humoral immune response they induce at the population scale remains unclear. Here, in a prospective, longitudinal, cohort-study, including 1245 hospital care workers and 146 nursing home residents scheduled for BNT162b2 vaccination, together covering adult ages from 19 to 99 years, we analyse seroconversion to SARS-CoV-2 spike protein and amount of spike-specific IgG, IgM and IgA before vaccination, and 3-5 weeks after each dose. We show that immunogenicity after a single vaccine dose is biased to IgG, heterogeneous and reduced with increasing age. The second vaccine dose normalizes IgG seroconversion in all age strata. These findings indicate two dose mRNA vaccines is required to reach population scale humoral immunity. The results advocate for the interval between the two doses not to be extended, and for serological monitoring of elderly and immunosuppressed vaccinees.
While mRNA vaccines authorised for emergency use are administrated worldwide in an effort to contain the COVID19 crisis, little is known about the heterogeneity of the immune response they induce. Here, we report the first 6 weeks of a longitudinal study that quantifies the humoral immune response to BNT162b2 mRNA COVID-19 (Pfizer/BioNTech, Comirnaty) in 1245 health care providers, the Lx1000HCW-PZF cohort. We reveal a striking inter-individual variation 3 weeks after the 1st dose administration that only in part related to age and sex. While population homogeneity in robust IgG responses was reached upon 2nd dose administration, IgM and IgA levels remain low and heterogenous. Our findings of isotypic and heterogenous antibody responses to Comirnaty highlight the need for evaluating the efficacy of COVID-19 mRNA vaccine in preventing infection aside disease, and - contrary to what has been proposed - advocate for the interval between the two doses not to be extended.
Introduction
Kidney transplant patients (KT) are at high risk for severe COVID‐19 and presented attenuated antibody responses to vaccination when compared to immunocompetent individuals. Torquetenovirus (TTV) has recently gained attention as a potential surrogate marker of the net state of immunosuppression. We evaluated the association between pre‐vaccination TTV viral load and anti‐spike total antibody response to SARS‐CoV‐2 vaccination in KT.
Material and Methods
The 114 adult KT recipients enrolled in this prospective single‐center cohort study received two doses of SARS‐CoV‐2 mRNA BNT162b2 vaccine. Serum samples were collected immediately before vaccination at the days when patients received both the first (T0) and the second dose (T1) and 16–45 days after the second dose (T2). Primary endpoint was the development of anti‐spike total antibodies after vaccination. Demographic, clinical, and laboratorial parameters were compared between patients with and without detectable SARS‐CoV‐2 antibodies at T2.
Results
Ninety‐nine patients (86.8%) were naïve for SARS‐CoV‐2 before vaccination. Fifty‐six (56.6%) patients developed anti‐spike total antibodies at T2. The use of mTOR inhibitors was associated with a favorable response (p = .005); conversely, mycophenolic acid (MPA) was associated with a negative response (p = .006). In a multivariable model, the presence of TTV at T0 ≥ 3.36 log10 cp/ml was associated with unfavorable vaccine response (OR: 5.40; 95% CI: 1.47–19.80; p = .011), after adjusting for age and eGFR at T0.
Conclusions
Higher TTV viral loads before vaccination are associated with reduced anti‐spike total antibody response in SARS‐CoV‐2 mRNA BNT162b2 vaccinated KT patients. The association between TTV viral load and vaccine response may be an added‐value in the optimization of vaccination regimens in KT.
Kidney transplant (KT) recipients are at an increased risk for severe COVID‐19 because of their immunosuppressed state. A 42‐year‐old KT patient was diagnosed with COVID‐19 three months after KT. Despite lymphopenia and several risk factors, he had a mild disease course. Nasopharyngeal real‐time reverse transcriptase polymerase chain reaction for SARS‐CoV‐2 became negative 48 days after detection. SARS‑CoV‑2 IgG antibodies became negative after day 40. TTV DNA load increased with the onset COVID‐19 and reduced after its resolution. This is the first report where TTV DNA load was measured during the course of COVID‐19.
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