key: cord-0855104-cvxbwrv7
authors: Terpos, Evangelos; Trougakos, Ioannis P.; Karalis, Vangelis; Ntanasis‐Stathopoulos, Ioannis; Sklirou, Aimilia D.; Bagratuni, Tina; Papanagnou, Eleni‐Dimitra; Patseas, Dimitrios; Gumeni, Sentiljana; Malandrakis, Panagiotis; Korompoki, Eleni; Dimopoulos, Meletios A.
title: Comparison of neutralizing antibody responses against SARS‐CoV‐2 in healthy volunteers who received the BNT162b2 mRNA or the AZD1222 vaccine: Should the second AZD1222 vaccine dose be given earlier?
date: 2021-06-02
journal: Am J Hematol
DOI: 10.1002/ajh.26248
sha: 7e30a2ba85d59ba3f4d75e1753a286fc7eba38d4
doc_id: 855104
cord_uid: cvxbwrv7

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Piscataway, NJ, USA) was used, which allows indirect detection of potential SARS-CoV-2 NAbs in blood by testing antibody-mediated inhibition of SARS-CoV-2 RBD binding to the human host receptor angiotensin converting enzyme 2. The time points for blood collection and serum isolation were day 1 (D1, before the first Pfizer or AZ shot), D22

(before the second shot, only for Pfizer vaccine; second shot of AZ vaccine was scheduled for 12 weeks after the first shot), and D50 (4 weeks after the second Pfizer shot, 7 weeks after the first AZ shot).

After venipuncture, serum was separated within 4 h of blood collection and stored at À80°C until the day of measurement. Stored samples from different time points of the same donor were measured in parallel assays.

After data collection, statistical analysis was performed in the Python programming language (v. 3.9.2). The analysis included descriptive statistics and statistical comparisons between groups.

Prior to statistical comparisons, a normality test of the data distributions was performed using the Shapiro-Wilk criterion. In the case of normally distributed data, parametric comparison methods were used, while if all or one of the compared groups deviated from normality, non-parametric methods were used. In all cases in this analysis, either one or all of the groups deviated from the normal distribution, so two-group and multiple-group analyses were performed using the nonparametric Mann-Whitney U test and Kruskal-Wallis H test, respectively. Because comparisons were between different groups of subjects, namely men versus women or Pfizer vs. AZ vaccinated subjects, independent group comparisons were performed. For comparisons of nominal variables (e.g., occurrence of an adverse event with vaccine type), chi-square analysis was used. In all cases, the significance level was set at 5% and a result was considered significant if the estimated p-value (p) was below the significance level. The median inhibition values were 43.6% and 35.0% for the Pfizer and AZ groups, respectively. This difference was found to be statistically significant (p = 0.031), indicating a slightly higher percentage inhibition of SARS-CoV-2 by the Pfizer vaccine compared to the AZ vaccine. Overall, for the Pfizer group, seven (8.9%) and seventeen (21.8%) subjects had NAbs titers greater than 75% and less than 30%, respectively. For the AZ group, the number of subjects who had inhibition less than 30% was 32 (43.8%), while five of them (6.8%) had inhibition greater than 75%.

At D50, the difference in inhibition between Pfizer's vaccine and AZ was even greater, reaching a median inhibition value of 95.6% in the case of Pfizer compared to the median estimate of 41.1% for AZ (p < 0.001). In this point we have to stress that the Pfizer group had received the second vaccine dose four weeks before (on D22), while the AZ group had received only the first vaccination dose (on D1). In the case of Pfizer's vaccine, half of the subjects developed inhibition greater than 95%, the majority of them (73 subjects or 93.6%) had NAbs inhibitory titers greater than 75%, while only two (2.6%) were classified as negative (less than 30%). In the AZ group, the number of subjects with inhibition greater than 75% was eight (10.9%), while eighteen subjects (24.6%) had NAbs inhibition less than 30%.

A similar analysis was also performed with respect to gender to identify possible gender differences in the development of percentage inhibition of SARS-CoV-2 between the two vaccines. It was found that both males and females in the Pfizer group developed inhibition levels significantly faster compared to AZ group (p-values equal to 0.032 and 0.027 for males and females, respectively) from day 1 to 22, after only one vaccination with each vaccine, respectively.

The possible influence of BMI on NAbs titers was also investigated. In the Pfizer group, 33.7% had normal weight, 48.2% were overweight, and 18.1% were obese. In the AZ group, 28.4% of subjects had normal weight, 40.7% were overweight, and 30.9% were obese. No significant differences were observed between BMI groups Despite the relatively small sample size, this study showed that

NAbs inhibitory values reached moderate levels with Pfizer and AZ at three weeks after the first vaccination, with slightly higher values after vaccination with Pfizer. At day 50, that is, 4 weeks after the second vaccination with Pfizer, the inhibition levels for Pfizer's vaccine became very high, with half of them showing inhibition of more than 95%, while the inhibition levels of AZ remain almost at the moderate levels of D22, as these patients had not received the second vaccine dose yet. Although many countries have opted for a 12-week interval between the two doses of AZ in order to increase the number of vaccinated people with at least one dose, 6 our results advocate for a shorter administration schedule, especially as more vaccines are becoming available. Furthermore, males and females treated with Pfizer vaccine achieved significantly faster viral inhibition at D22 than those treated with the AZ vaccine. BMI was found to have no significant effect on NAbs titers. Finally, it was found that the AZ vaccine was significantly associated with a higher incidence of mild adverse events compared to the Pfizer vaccine. 

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial

Age-dependent and gender-dependent antibody responses against SARS-CoV-2 in health workers and octogenarians after vaccination with the BNT162b2 mRNA vaccine

Low Neutralizing Antibody Responses Against SARS-CoV-2 in Elderly Myeloma Patients After the First BNT162b2 Vaccine Dose

Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials

The authors declare no relevant conflict of interest.

The data that support the findings of this study are available from the corresponding author upon reasonable request.