Spike-specific antibody responses are 2.9-fold higher after dual vaccination with BNT162b2 compared to ChAdOx1 in older donors
131 donors, aged 80+ years age and who were living in the community, were recruited to the study. Blood samples were taken at 2-3 weeks after the second vaccine. Spike-specific antibody responses were assessed using quantitative Roche spike-specific ELISA and positive responses were seen in all donors after the BNT162b2 (n=54) or ChAdOx1 (n=77) vaccine respectively (Figure 1). However, the median spike-specific antibody level was 2.9-times higher in donors who had received BNT162b2 vaccination. Specifically, median values were 4100 u/ml after BNT162b2 (IQR 1912 -8613) compared to 1416 (IQR 480-2643) in ChAdOx1 vaccinees. Exclusion of 4 donors with serological evidence of previous SARS-CoV-2 infection, which is known to strongly boost vaccine responses(13), led to values of 4030 u/ml and 1405 u/ml respectively.
Elevated spike-specific antibody responses after dual BNT162b2 vaccination reflect enhanced incremental response to the second vaccine
In addition to blood samples taken after the second vaccine we also had access to matched patient samples that had been taken at 5-6 weeks after the first vaccine. Antibody and cellular analysis of these samples has been reported previously and demonstrated that antibody levels were comparable after a single dose of either BNT162b2 or ChAdOx1 vaccine (14). As such we next went on to determine the pattern of incremental antibody response after the second vaccine within this cohort.
For all BNT162b2 vaccinees the median antibody level was 21 after the first vaccine (IQR 6.2-76.5) which rose to 4100 after the second vaccine. As such the booster vaccine led to a 197 fold increase in antibody response. One donor had serological evidence of previous SARS-CoV-2 infection and here these values were 47,100 and 58,800 respectively. Exclusion of this donor allowed assessment of vaccine responses in 53 infection-naïve donors where median antibody responses were 19 (IQR 6.2-68) and 4030 (IQR 1890 -8530) respectively after the first and second vaccines, representing a 214-fold increase (P<0.0001)
For ChAdOx1 vaccinees, paired samples were available for 77 donors of whom 3 had serological evidence of previous infection with SARS-CoV-2. Within the total cohort median antibody levels rose from 21 (IQR 7-60) to 1416 (IQR 480-2640) between first and second vaccines, a 67-fold increase p<0.0001 (Wilcoxon). For the three donors with previous infection these values were 12,400 (IQR 2680 – 20200) and 10,350 (4500 -21240) respectively. Values within the 74 donors without previous infection were 20 (IQR 6.4 – 53) and 1405 (IQR 470 - 2540) respectively, representing a 70-fold increase (p<0.0001).
These data show that the second dose of either vaccine strongly boosts antibody responses. However, within infection-naïve donors this relative increment is three-fold higher with the BNT162b2 vaccine which explains the higher final responses after dual vaccination.
Spike-specific cellular responses are 1.7-fold higher after dual vaccination with ChAdOx1 compared with BNT162b2
Our interim analysis of immune response at 5 weeks after first vaccine in this cohort had shown higher spike-specific cellular responses after the ChAdOx1 vaccine (14) and we next assessed relative responses after dual vaccination using interferon-g ELISpot.
Within BNT162b2 vaccinees, 51 of the 54 donors had paired cellular responses for analysis. The proportion of donors who showed a cellular response above the threshold rose from 9.8% (5/51) to 33.3% (17/51) after first and second vaccination respectively. The median level of response increased from 4 to 14 spots per million PBMC after excluding the single donor with previous natural infection (P<0.0001).
For donors who received ChAdOx1 vaccination, paired T cell results were available for 76 of the 77 donors. The proportion of positive responses increased from 34.2% (26/76) after the first vaccine to 48.6% (37/76) after second vaccine. After excluding donors with evidence of natural infection, the median absolute counts increased from 12 to 20 spots per million after first and second vaccine (p=0.0014).
These findings indicate that ChAdOx1 stimulates a stronger spike-specific cellular response in older people although the relative incremental advantage of this vaccine above BNT162b2 falls from 3-fold to 1.4-fold between the first and second doses of vaccine.
Spike-specific immune responses after dual vaccination in donors aged 80+ years are comparable to those seen in younger donors
Vaccine-induced immune responses are often suboptimal in older people and this may reflect the impact of immune senescence. As such, we then compared our findings in donors aged 80 years and above with a population of donors aged between 42 and 79 years of age in whom antibody and cellular responses were measured in a similar way.
Of note, immune responses at both timepoints were comparable between both cohorts with no significant impairment of antibody or cellular responses in older people. In donors without previous natural infection, median antibody responses after BNT162b2 for younger and older cohorts were 46 and 19 after the first vaccine (p=0.57) and 7026 and 4030 after second vaccine respectively (p=0.1). For ChAdOx1 the comparable values were 25 and 20 (p=0.08) and 949 and 1405 respectively (p=0.96). These results indicate a trend towards slightly lower antibody responses after dual vaccination with BNT162b2 in older people.
T cell assays were available after the second vaccine in the younger cohort. Within infection-naïve donors the median T cell responses after BNT162b2 in the older and younger cohorts was 14 spots/million in both groups whilst after ChADOX1 these values were equivalent at 20 spots/million.
As such these findings show that dual homologous vaccination with either BNT162b2 or ChAdOx1 is highly effective for induction of spike-specific immune responses in older people and largely overcomes any significant effect of immune senescence.