Post by Admin on Sept 10, 2020 4:52:19 GMT
Results
Between June 18 and Aug 3, 2020, 76 healthy adults were enrolled to the two studies from the volunteer register (figure 1). 43 adults were selected at the beginning of each study from the volunteer registry; 38 participants were included in each study and five people were kept as backup volunteers in case of dropouts (two for phase 1 and three for phase 2). Nine participants in each study received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received sequential injections of rAd26-S (on day 0) and rAd5-S (on day 21) in phase 2. All volunteers in the main group were analysed and additional volunteers from the backup groups were not needed. Thus, in each study, 38 volunteers were vaccinated. More men than women took part in the study (table 1).
Figure 1 Trial profile
Table 1 Baseline characteristics
Gam-COVID-Vac Gam-COVID-Vac-Lyo
rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20) rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20)
Sex
Male 9 (100%) 9 (100%) 14 (70%) 5 (56%) 2 (22%) 14 (70%)
Female 0 0 6 (30%) 4 (44%) 7 (78%) 6 (30%)
Height, m 1·8 (0·1) 1·8 (0·1) 1·7 (0·1) 1·7 (0·1) 1·7 (0·1) 1·8 (0·1)
Bodyweight, kg 80·6 (6·0) 83·4 (13·8) 74·6 (12·5) 72·1 (13·1) 65·8 (9·4) 72·0 (12·6)
Age, years 27·8 (5·1) 25·3 (6·1) 26·4 (4·4) 31·4 (8·2) 27·0 (7·7) 26·7 (5·8)
Ethnicity
White 9 (100%) 9 (100%) 20 (100%) 8 (89%) 9 (100%) 19 (95%)
Asian 0 0 0 1 (11%) 0 1 (5%)
SARS-CoV-2 IgM and IgG negative 9 (100%) 9 (100%) 20 (100%) 9 (100%) 9 (100%) 20 (100%)
Data are n (%) or mean (SD). Gam-COVID-Vac=frozen vaccine formulation. Gam-COVID-Vac-Lyo=lyophilised vaccine formulation. rAd26-S=recombinant adenovirus type 26 carrying the gene for SARS-CoV-2 full-length glycoprotein S. rAd5-S=recombinant adenovirus type 5 carrying the gene for SARS-CoV-2 full-length glycoprotein S. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
In both studies, systemic and local reactions (table 2) and changes in laboratory variables (appendix pp 3–7) were among the adverse events reported. The most common systemic and local reactions were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most systemic and local reactions were mild. Changes in laboratory variables were mild and transient. In volunteers who received both vaccine components (rAd26-S and rAd5-S), most adverse events occurred after the second vaccination (appendix pp 5–7). No adverse events, either during phase 1 or phase 2, led to withdrawal of a participant from the study or withdrawal of study drug. In general, adverse events identified during phase 1 and phase 2 of both studies were characteristic of other vaccines (particularly those based on recombinant viral vectors). No serious adverse events were reported and all participants were clinically well throughout the study.
Table 2 Systemic and local adverse events
Gam-COVID-Vac Gam-COVID-Vac-Lyo
rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20) rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20)
Systemic reactions
Hyperthermia
Mild (37·0–38·4°C; grade 1) 8 (89%) 2 (22%) 19 (95%) 1 (11%) 1 (11%) 6 (30%)
Moderate (38·5–38·9°C; grade 2) 0 1 (11%) 1 (5%) 0 0 1 (5%)
Headache
Mild (grade 1) 6 (67%) 3 (33%) 9 (45%) 3 (33%) 4 (44%) 5 (25%)
Moderate (grade 2) 0 0 2 (10%) 0 0 0
Asthenia
Mild (grade 1) 3 (33%) 3 (33%) 11 (55%) 0 0 4 (20%)
Muscle and joint pain
Mild (grade 1) 3 (33%) 2 (22%) 4 (20%) 1 (11%) 2 (22%) 4 (20%)
Moderate (grade 2) 0 0 1 (5%) 0 0 2 (10%)
Heartbeat (subjective palpitation)
Mild (grade 1) 3 (33%) 1 (11%) 0 0 0 0
Diarrhoea
Mild (grade 1) 1 (11%) 0 3 (15%) 0 0 0
Rhinorrhoea
Mild (grade 1) 0 0 4 (20%) 0 0 0
Loss of appetite
Mild (grade 1) 2 (22%) 0 1 (5%) 0 0 0
Pain in the oropharynx (pharyngalgia)
Mild (grade 1) 0 1 (11%) 1 (5%) 0 0 0
Malaise
Mild (grade 1) 0 0 2 (10%) 0 0 0
Sore throat (throat irritation)
Mild (grade 1) 0 0 2 (10%) 0 0 0
Hives
Mild (grade 1) 1 (11%) 0 0 0 0 0
Nasal congestion
Mild (grade 1) 0 0 1 (5%) 0 0 0
Cough
Mild (grade 1) 0 0 1 (5%) 0 0 0
Sneezing
Mild (grade 1) 0 0 1 (5%) 0 0 0
Changes in laboratory variables
Mild (grade 1) 9 (100%) 8 (89%) 20 (100%) 7 (78%) 6 (67%) 18 (90%)
Moderate (grade 2) 0 1 (11%) 0 0 0 0
Local reactions
Pain
Mild (grade 1) 7 (78%) 5 (56%) 8 (40%) 5 (56%) 7 (78%) 12 (60%)
Oedema
Mild (grade 1) 0 0 0 2 (22%) 1 (11%) 0
Hyperthermia
Mild (grade 1) 0 0 2 (10%) 0 1 (11%) 0
Itch
Mild (grade 1) 1 (11%) 0 0 0 0 0
Swelling
Mild (grade 1) 0 0 1 (5%) 0 0 0
The table shows the total number (%) of volunteers who developed adverse events, according to severity (mild [grade 1], moderate [grade 2], and severe [grade 3]). No grade 3 adverse events were reported. Some volunteers had adverse events of two degrees of severity. Gam-COVID-Vac=frozen vaccine formulation. Gam-COVID-Vac-Lyo=lyophilised vaccine formulation. rAd26-S=recombinant adenovirus type 26 carrying the gene for SARS-CoV-2 full-length glycoprotein S. rAd5-S=recombinant adenovirus type 5 carrying the gene for SARS-CoV-2 full-length glycoprotein S. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
During phase 1 of both studies (administration of either rAd26-S or rAd5-S alone), SARS-CoV-2 RBD-specific IgGs were detected on day 14 in 88·9% of participants after administration of rAd26-S and in 84·2% of participants after administration of rAd5-S (combined data for both the lyophilised and frozen vaccine formulations); beginning from day 21, SARS-CoV-2 RBD-specific IgGs were detected in 100% of vaccinated participants. During phase 2, SARS-CoV-2 RBD-specific IgGs were detected in 85·0% of participants on day 14 (after priming with rAd26-S) and in 100% of participants from day 21 (geometric mean titre [GMT] 1629 with the frozen formulation [Gam-COVID-Vac] and 951 with the lyophilised formulation [Gam-COVID-Vac-Lyo]; figure 2). Boosting with rAd5-S led to an increase in SARS-CoV-2 RBD-specific IgG titres; 7 days after boost, GMTs had increased to 3442 with Gam-COVID-Vac (p<0·0001 at day 28 vs day 21) and 5322 with Gam-COVID-Vac-Lyo (p<0·0001 at day 28 vs day 21). On day 42, GMTs of SARS-CoV-2 RBD-specific IgGs were 14 703 with Gam-COVID-Vac and 11 143 with Gam-COVID-Vac-Lyo (figure 2). On day 28 after vaccination with rAd26-S only (in phase 1), SARS-CoV-2 RBD-specific GMTs were significantly lower than in volunteers who had prime-boost vaccination (in phase 2): 1866 after rAd26-S of Gam-COVID-Vac (p=0·0047) and 1372 after rAd26-S of Gam-COVID-Vac-Lyo (p=0·0042). SARS-CoV-2 S1 subunit-specific IgGs were also assessed on days 0 and 42 in volunteers who received combined rAd26-S and rAd5-2 (in phase 2). GMTs were 53 006 with Gam-COVID-Vac and 51 200 with Gam-COVID-Vac-Lyo (p=0·78; appendix p 12). Analysis of neutralising antibodies to SARS-CoV-2 showed that only administration of both rAd26-S and rAd5-2 led to production of neutralising antibodies in 100% of participants (GMT 49·25 with Gam-COVID-Vac and 45·95 with Gam-COVID-Vac-Lyo at day 42), whereas administration of only rAd26-S led to a seroconversion rate of 61·1% (combined data for both the lyophilised and frozen vaccine formulations). Comparing data for antibody responses to SARS-CoV-2 at days 28 and 42 with data for antibody responses in convalescent plasma showed that post-vaccination ELISA titres were significantly higher than were titres after COVID-19 (for both days 28 and 42, p<0·0001), whereas significant differences in neutralising antibodies were not seen (p=0·55; figure 2). We also analysed the correlation between SARS-CoV-2 RBD ELISA titres and neutralising antibody titres and noted a strong correlation between these variables (r=0·82, 95% CI 0·77–0·86; p<0·0001; appendix p 13).
Figure 2 Humoral immune response
When analysing antigen-specific IgGs, the seroconversion rate was 100% for both vaccine formulations on days 28 and 42 of the study, and when analysing neutralising antibody responses, seroconversion was 100% on day 42 of the study for both vaccine formulations. Seroconversion rates on days 0, 14, 28, and 42 (in phase 2) are presented in the appendix (pp 8–11). Descriptive statistics for humoral immune responses are presented in the appendix (pp 8–11).
Cellular immune responses showed formation of antigen-specific cells of both T-helper (CD4+) and T-killer (CD8+) cells, and an increase in the concentration of interferon-γ secretion in peripheral blood mononuclear cells, in 100% of volunteers (figure 3).
Cells from vaccinated participants proliferated significantly in response to glycoprotein S, particularly on day 28. The number of participants with CD4+ and CD8+ proliferative responses to antigen are shown in the appendix (p 14). Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+ with the frozen formulation (Gam-COVID-Vac), and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilised formulation (Gam-COVID-Vac-Lyo). The mononuclear cell response was evaluated on days 0, 14, and 28 by interferon-γ secretion and reported as fold increase in secretion on exposure to glycoprotein S of SARS-CoV-2 (figure 3). The number of participants with interferon-γ response to antigen are shown in the appendix (p 15). Descriptive statistics for cellular immune responses are presented in the appendix (pp 16–21).
Figure 3 Cell-mediated immune response to SARS-CoV-2 glycoprotein
To investigate the effect of the pre-existing immune response to adenoviral vectors, neutralising antibodies to recombinant vectors were measured in all participants on days 0 and 28 in both studies (figure 4). After one injection of vaccine components, not only is an immune response to target antigen formed but also an immune response is seen to components of the vaccine vector.
Further, a correlation analysis was done to compare the level of neutralising antibodies to recombinant vectors with the level of antigen-specific antibodies (appendix p 22). No significant correlation was noted between the titre of neutralising antibodies to recombinant viral vectors on day 0 and the titre of RBD-specific IgGs in serum samples of participants on days 14, 21, and 28 from the start of vaccination in participants in phase 1 of each study and on days 14, 21, 28, and 42 from the start of vaccination in participants in phase 2 of each study. Moreover, formation of cross-reactive neutralising antibodies to vectors rAd26 and rAd5 was analysed. Administration of rAd26 did not increase the titre of neutralising antibodies to rAd5 on day 28, and vice versa, which indicates the absence of cross-reactivity with respect to vaccine components (figure 4). Thus, the presence of a pre-existing immune response to the components of vaccine vectors rAd26 and rAd5 does not affect the titre of RBD-specific antibodies in the serum of participants.
Figure 4 Neutralising antibody response to rAd26 and rAd5 vectors after immunisation
Between June 18 and Aug 3, 2020, 76 healthy adults were enrolled to the two studies from the volunteer register (figure 1). 43 adults were selected at the beginning of each study from the volunteer registry; 38 participants were included in each study and five people were kept as backup volunteers in case of dropouts (two for phase 1 and three for phase 2). Nine participants in each study received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received sequential injections of rAd26-S (on day 0) and rAd5-S (on day 21) in phase 2. All volunteers in the main group were analysed and additional volunteers from the backup groups were not needed. Thus, in each study, 38 volunteers were vaccinated. More men than women took part in the study (table 1).
Figure 1 Trial profile
Table 1 Baseline characteristics
Gam-COVID-Vac Gam-COVID-Vac-Lyo
rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20) rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20)
Sex
Male 9 (100%) 9 (100%) 14 (70%) 5 (56%) 2 (22%) 14 (70%)
Female 0 0 6 (30%) 4 (44%) 7 (78%) 6 (30%)
Height, m 1·8 (0·1) 1·8 (0·1) 1·7 (0·1) 1·7 (0·1) 1·7 (0·1) 1·8 (0·1)
Bodyweight, kg 80·6 (6·0) 83·4 (13·8) 74·6 (12·5) 72·1 (13·1) 65·8 (9·4) 72·0 (12·6)
Age, years 27·8 (5·1) 25·3 (6·1) 26·4 (4·4) 31·4 (8·2) 27·0 (7·7) 26·7 (5·8)
Ethnicity
White 9 (100%) 9 (100%) 20 (100%) 8 (89%) 9 (100%) 19 (95%)
Asian 0 0 0 1 (11%) 0 1 (5%)
SARS-CoV-2 IgM and IgG negative 9 (100%) 9 (100%) 20 (100%) 9 (100%) 9 (100%) 20 (100%)
Data are n (%) or mean (SD). Gam-COVID-Vac=frozen vaccine formulation. Gam-COVID-Vac-Lyo=lyophilised vaccine formulation. rAd26-S=recombinant adenovirus type 26 carrying the gene for SARS-CoV-2 full-length glycoprotein S. rAd5-S=recombinant adenovirus type 5 carrying the gene for SARS-CoV-2 full-length glycoprotein S. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
In both studies, systemic and local reactions (table 2) and changes in laboratory variables (appendix pp 3–7) were among the adverse events reported. The most common systemic and local reactions were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most systemic and local reactions were mild. Changes in laboratory variables were mild and transient. In volunteers who received both vaccine components (rAd26-S and rAd5-S), most adverse events occurred after the second vaccination (appendix pp 5–7). No adverse events, either during phase 1 or phase 2, led to withdrawal of a participant from the study or withdrawal of study drug. In general, adverse events identified during phase 1 and phase 2 of both studies were characteristic of other vaccines (particularly those based on recombinant viral vectors). No serious adverse events were reported and all participants were clinically well throughout the study.
Table 2 Systemic and local adverse events
Gam-COVID-Vac Gam-COVID-Vac-Lyo
rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20) rAd26-S (n=9) rAd5-S (n=9) rAd26-S plus rAd5-S (n=20)
Systemic reactions
Hyperthermia
Mild (37·0–38·4°C; grade 1) 8 (89%) 2 (22%) 19 (95%) 1 (11%) 1 (11%) 6 (30%)
Moderate (38·5–38·9°C; grade 2) 0 1 (11%) 1 (5%) 0 0 1 (5%)
Headache
Mild (grade 1) 6 (67%) 3 (33%) 9 (45%) 3 (33%) 4 (44%) 5 (25%)
Moderate (grade 2) 0 0 2 (10%) 0 0 0
Asthenia
Mild (grade 1) 3 (33%) 3 (33%) 11 (55%) 0 0 4 (20%)
Muscle and joint pain
Mild (grade 1) 3 (33%) 2 (22%) 4 (20%) 1 (11%) 2 (22%) 4 (20%)
Moderate (grade 2) 0 0 1 (5%) 0 0 2 (10%)
Heartbeat (subjective palpitation)
Mild (grade 1) 3 (33%) 1 (11%) 0 0 0 0
Diarrhoea
Mild (grade 1) 1 (11%) 0 3 (15%) 0 0 0
Rhinorrhoea
Mild (grade 1) 0 0 4 (20%) 0 0 0
Loss of appetite
Mild (grade 1) 2 (22%) 0 1 (5%) 0 0 0
Pain in the oropharynx (pharyngalgia)
Mild (grade 1) 0 1 (11%) 1 (5%) 0 0 0
Malaise
Mild (grade 1) 0 0 2 (10%) 0 0 0
Sore throat (throat irritation)
Mild (grade 1) 0 0 2 (10%) 0 0 0
Hives
Mild (grade 1) 1 (11%) 0 0 0 0 0
Nasal congestion
Mild (grade 1) 0 0 1 (5%) 0 0 0
Cough
Mild (grade 1) 0 0 1 (5%) 0 0 0
Sneezing
Mild (grade 1) 0 0 1 (5%) 0 0 0
Changes in laboratory variables
Mild (grade 1) 9 (100%) 8 (89%) 20 (100%) 7 (78%) 6 (67%) 18 (90%)
Moderate (grade 2) 0 1 (11%) 0 0 0 0
Local reactions
Pain
Mild (grade 1) 7 (78%) 5 (56%) 8 (40%) 5 (56%) 7 (78%) 12 (60%)
Oedema
Mild (grade 1) 0 0 0 2 (22%) 1 (11%) 0
Hyperthermia
Mild (grade 1) 0 0 2 (10%) 0 1 (11%) 0
Itch
Mild (grade 1) 1 (11%) 0 0 0 0 0
Swelling
Mild (grade 1) 0 0 1 (5%) 0 0 0
The table shows the total number (%) of volunteers who developed adverse events, according to severity (mild [grade 1], moderate [grade 2], and severe [grade 3]). No grade 3 adverse events were reported. Some volunteers had adverse events of two degrees of severity. Gam-COVID-Vac=frozen vaccine formulation. Gam-COVID-Vac-Lyo=lyophilised vaccine formulation. rAd26-S=recombinant adenovirus type 26 carrying the gene for SARS-CoV-2 full-length glycoprotein S. rAd5-S=recombinant adenovirus type 5 carrying the gene for SARS-CoV-2 full-length glycoprotein S. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
During phase 1 of both studies (administration of either rAd26-S or rAd5-S alone), SARS-CoV-2 RBD-specific IgGs were detected on day 14 in 88·9% of participants after administration of rAd26-S and in 84·2% of participants after administration of rAd5-S (combined data for both the lyophilised and frozen vaccine formulations); beginning from day 21, SARS-CoV-2 RBD-specific IgGs were detected in 100% of vaccinated participants. During phase 2, SARS-CoV-2 RBD-specific IgGs were detected in 85·0% of participants on day 14 (after priming with rAd26-S) and in 100% of participants from day 21 (geometric mean titre [GMT] 1629 with the frozen formulation [Gam-COVID-Vac] and 951 with the lyophilised formulation [Gam-COVID-Vac-Lyo]; figure 2). Boosting with rAd5-S led to an increase in SARS-CoV-2 RBD-specific IgG titres; 7 days after boost, GMTs had increased to 3442 with Gam-COVID-Vac (p<0·0001 at day 28 vs day 21) and 5322 with Gam-COVID-Vac-Lyo (p<0·0001 at day 28 vs day 21). On day 42, GMTs of SARS-CoV-2 RBD-specific IgGs were 14 703 with Gam-COVID-Vac and 11 143 with Gam-COVID-Vac-Lyo (figure 2). On day 28 after vaccination with rAd26-S only (in phase 1), SARS-CoV-2 RBD-specific GMTs were significantly lower than in volunteers who had prime-boost vaccination (in phase 2): 1866 after rAd26-S of Gam-COVID-Vac (p=0·0047) and 1372 after rAd26-S of Gam-COVID-Vac-Lyo (p=0·0042). SARS-CoV-2 S1 subunit-specific IgGs were also assessed on days 0 and 42 in volunteers who received combined rAd26-S and rAd5-2 (in phase 2). GMTs were 53 006 with Gam-COVID-Vac and 51 200 with Gam-COVID-Vac-Lyo (p=0·78; appendix p 12). Analysis of neutralising antibodies to SARS-CoV-2 showed that only administration of both rAd26-S and rAd5-2 led to production of neutralising antibodies in 100% of participants (GMT 49·25 with Gam-COVID-Vac and 45·95 with Gam-COVID-Vac-Lyo at day 42), whereas administration of only rAd26-S led to a seroconversion rate of 61·1% (combined data for both the lyophilised and frozen vaccine formulations). Comparing data for antibody responses to SARS-CoV-2 at days 28 and 42 with data for antibody responses in convalescent plasma showed that post-vaccination ELISA titres were significantly higher than were titres after COVID-19 (for both days 28 and 42, p<0·0001), whereas significant differences in neutralising antibodies were not seen (p=0·55; figure 2). We also analysed the correlation between SARS-CoV-2 RBD ELISA titres and neutralising antibody titres and noted a strong correlation between these variables (r=0·82, 95% CI 0·77–0·86; p<0·0001; appendix p 13).
Figure 2 Humoral immune response
When analysing antigen-specific IgGs, the seroconversion rate was 100% for both vaccine formulations on days 28 and 42 of the study, and when analysing neutralising antibody responses, seroconversion was 100% on day 42 of the study for both vaccine formulations. Seroconversion rates on days 0, 14, 28, and 42 (in phase 2) are presented in the appendix (pp 8–11). Descriptive statistics for humoral immune responses are presented in the appendix (pp 8–11).
Cellular immune responses showed formation of antigen-specific cells of both T-helper (CD4+) and T-killer (CD8+) cells, and an increase in the concentration of interferon-γ secretion in peripheral blood mononuclear cells, in 100% of volunteers (figure 3).
Cells from vaccinated participants proliferated significantly in response to glycoprotein S, particularly on day 28. The number of participants with CD4+ and CD8+ proliferative responses to antigen are shown in the appendix (p 14). Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+ with the frozen formulation (Gam-COVID-Vac), and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilised formulation (Gam-COVID-Vac-Lyo). The mononuclear cell response was evaluated on days 0, 14, and 28 by interferon-γ secretion and reported as fold increase in secretion on exposure to glycoprotein S of SARS-CoV-2 (figure 3). The number of participants with interferon-γ response to antigen are shown in the appendix (p 15). Descriptive statistics for cellular immune responses are presented in the appendix (pp 16–21).
Figure 3 Cell-mediated immune response to SARS-CoV-2 glycoprotein
To investigate the effect of the pre-existing immune response to adenoviral vectors, neutralising antibodies to recombinant vectors were measured in all participants on days 0 and 28 in both studies (figure 4). After one injection of vaccine components, not only is an immune response to target antigen formed but also an immune response is seen to components of the vaccine vector.
Further, a correlation analysis was done to compare the level of neutralising antibodies to recombinant vectors with the level of antigen-specific antibodies (appendix p 22). No significant correlation was noted between the titre of neutralising antibodies to recombinant viral vectors on day 0 and the titre of RBD-specific IgGs in serum samples of participants on days 14, 21, and 28 from the start of vaccination in participants in phase 1 of each study and on days 14, 21, 28, and 42 from the start of vaccination in participants in phase 2 of each study. Moreover, formation of cross-reactive neutralising antibodies to vectors rAd26 and rAd5 was analysed. Administration of rAd26 did not increase the titre of neutralising antibodies to rAd5 on day 28, and vice versa, which indicates the absence of cross-reactivity with respect to vaccine components (figure 4). Thus, the presence of a pre-existing immune response to the components of vaccine vectors rAd26 and rAd5 does not affect the titre of RBD-specific antibodies in the serum of participants.
Figure 4 Neutralising antibody response to rAd26 and rAd5 vectors after immunisation