Demographics and vaccination coverage
A total of 702 individuals participated in this study. Descriptive data for the study population are summarized in Table 1. The median (IQR) age was 43 years (33-59), 332 participants (47.3%) were men and 370 (52.7%) participants were women. Overall, 148 (21.1 %) participants with a SARS-CoV-2 positive PCR-test or a positive nose/throat swab rapid test were considered to have previously been infected with SARS-CoV-2 regardless of whether they had reported previous symptoms, while 39 out of the 148 had received one or two doses of a licensed vaccine. From a total of 554 participants without evidence of previous infection, 339 had received either one or two doses of a licensed vaccine, 2 participants had received 3 doses of Pfizer/BioNTech and 1 participant had received 3 doses of the Moderna vaccine. Based on these definitions, we initially categorized participants into three groups as follows: i) vaccinated without evidence of prior infection (n=342); ii) unvaccinated with evidence of prior infection (n=109), and iii) vaccinated with evidence of prior infection (n=39). Unvaccinated participants without evidence of prior infection (n=212) were used as the control group. We also categorized participants into three age groups namely the 18-45 years of age (n=385), 46-65 years of age (n=222), and > 66 years of age (n =95).
Table 2 summarizes the vaccination coverage in terms of vaccine type and the number of doses in individuals with or without evidence of prior infection with SARS-CoV-2. It is shown that more than 63.5 % of the participants (242 of 381) received one, two, or three doses of the Pfizer/BioNTech vaccine. Due to the small number, individuals who received the Johnson and Johnson vaccine or 3 doses of either the Pfizer/BioNTech or the Moderna Vaccine were excluded from the subsequent analysis.
Antibodies against SARS-CoV-2 increased following vaccination or infection as illustrated in Fig. 1, while the levels of specific anti-spike IgG were significantly higher (p<0.001) in all three groups compared to the control group (Fig. 1). Specifically, without evidence of prior infection, anti-spike IgG antibodies were detected after vaccination in 312 of 342 (91.2 %) of participants. In the unvaccinated group with evidence of prior infection, antibodies were detected in 84 of 109 (77.1%) participants. Interestingly, in the vaccinated group with evidence of prior infection anti-spike IgG antibodies were detected in 100% of participants. Furthermore, this group (vaccinated with evidence of prior infection) also had the highest virus-specific IgG antibody levels detected as illustrated in Fig. 1. There was no statistical difference in anti-spike IgG antibodies levels between men and women in all groups as resulted by the Mann Whitney U test (data not shown).
We then analyzed the antibody levels in participants without evidence of prior infection who received at least one dose of a vaccine in the three age groups (Fig. 2A). After vaccination, anti-spike IgG antibodies were detected in 137 of 151 (90.7 %) of participants of the 18-45 years of age group. In the 46-65 years of age and >66 years of age groups, antibodies were detected in 106 of 112 (94.6 %) and 65 of 69 (94.2 %), respectively. Our analysis revealed that there were no statistically significant differences in specific anti-spike IgG levels among the three age groups (Fig. 2A).
We also compared the levels of vaccine-elicited IgG after the administration of one and two doses of the same vaccine (Fig. 2B). There was no statistically significant difference in anti-spike IgG levels between one dose and two doses of the Oxford-Astra Zeneca. Anti-spike IgG levels were significantly increased (p<0.05) following the second dose of the Moderna vaccine. Administration of a second dose of the Pfizer/BioNTech vaccine also resulted in the production of higher levels of IgG antibodies compared to the first dose, but these differences did not reach statistical significance. We then compared the levels of vaccine-elicited anti-spike IgG between the two different vaccine technologies, i.e., after the administration of i) one dose and ii) two doses of either an adenoviral-based vaccine (Oxford-Astra Zeneca) or an mRNA-based vaccine (Moderna or Pfizer-BioNTech). There was no statistically significant difference (p>0.05) in IgG levels between the groups who received a single dose of i) the Oxford- Astra Zeneca (n=33) or Moderna (n=10) vaccine and ii) the Oxford- Astra Zeneca (n=33) and the Pfizer-BioNTech (n=25) vaccine. There was also no statistically significant difference (p>0.05) in IgG levels between the groups who received a single dose of the Pfizer-BioNTech or Moderna vaccine. Interestingly, the IgG levels in the group who received a single dose of the Pfizer-BioNTech were significantly higher (p<0.01) compared to the group who received one dose of the Oxford-AstraZeneca Vaccine. Anti-Spike IgG levels were significantly higher (p<0.001) after two doses of Moderna (n=38) than after Astra-Zeneca (n=32). Vaccination with two doses of Pfizer/BioNTech (n=191) induced the production of significantly higher levels (p<0.0001) of IgG antibodies than those produced after administration of two doses of Astra-Zeneca. However, there was no statistically significant difference (p>0.05) in the levels of anti-Spike IgG antibodies between the groups vaccinated with two doses of the Moderna or two doses of Pfizer-BioNTech (Fig 2B).
Correlation of antibody levels post-vaccination with the age of the participants
Participants without evidence of prior infection who had received at least one dose of a vaccine were included in a subsequent analysis, to investigate associations between IgG levels and the age of participants regardless of the type/doses of vaccine given. The differences in vaccine response by age group are presented in Fig 3. There was no correlation between the anti-spike IgG levels and the age of participants in the 18-45 years (Fig. 3A) and 46-65 years groups (p<0.05) (Fig. 3B), however, the levels of IgG in the >66 years of age group were negatively and moderately correlated (r=-0.2454; p<0.05) with the age of participants (Fig 3C).
Comparison between the levels of SARS-CoV-2 antibodies elicited by SARS-CoV-2 vaccination and infection
As aforementioned, an important question is whether vaccine-induced responses are more potent and durable than those measured following natural infection. However, in the case of SARS-CoV-2, the extent to which infection can protect against subsequent reinfection remains unclear. Thus, we then sought to compare the levels of specific anti-SARs-CoV-2 IgG between vaccinated individuals without evidence of a previous infection with unvaccinated individuals with evidence of previous infection in the three age groups (Fig. 4). Our analysis revealed that the levels of anti-spike IgG antibodies in vaccinated participants without evidence of prior infection were significantly higher compared to unvaccinated participants with evidence of prior infection in the 18-45 and 46-65 age groups. However, there was no statistically significant difference between the vaccine-elicited and infection-elicited antibodies in the >66 years of age group. Moreover, antibody responses in younger unvaccinated participants (18-45 years of age) with evidence of prior infection was lower compared to older participants (46-65 and >66 years of age group), but these differences did not reach statistical significance (p>0.05).
Moreover, in those without evidence of prior infection who received at least one dose of a vaccine, there was no statistically significant difference in anti-spike IgG antibodies levels between men and women in all age groups as resulted by Mann Whitney U test (data not shown). Finally, in unvaccinated individuals with evidence of prior infection, there was no statistically significant difference in IgG levels between men and women in all age groups as resulted by the Mann Whitney U test (data not shown).
Time course of anti-spike IgG antibodies after vaccination with one dose
The time courses of the anti-spike IgG levels in individuals without evidence of previous infection who received one dose of a licensed vaccine are illustrated in Figure 5 (A-C). An increase in IgG levels was observed approximately 10 days post-vaccination regardless of the vaccine type (Fig. 5A). Vaccinated individuals who had received one dose of an mRNA-based vaccine (Moderna or Pfizer/BioNTech) developed antibodies 10 days post-vaccination (Fig. 5B), while high IgG titers were detected in individuals who received one dose of the Astra-Zeneca Vaccine (Fig 5C).
Time course of anti-spike IgG antibodies after vaccination and natural infection
The time courses of the anti-spike IgG levels (counting begins for the day of the first dose) in individuals without evidence of previous infection, who received two doses of a licensed vaccine (regardless of the vaccine type), as well as vaccinated and unvaccinated individuals with evidence of prior infection, are illustrated in Fig. 6.
Anti-spike IgG antibodies were detectable in 96% of participants with no prior infection who had received two doses of a vaccine, while antibody levels showed a slight decrease 120 post-vaccination (Fig 6A). Interestingly, antibody levels persisted in individuals with prior evidence of infection who received one dose or two doses of a vaccine (Fig 6B). Finally, in those with evidence of prior infection who have not been vaccinated, IgG levels showed a decrease approximately 120 days post-infection reaching the background levels 240 post-infection (Fig 6C). Taken together, these results revealed that vaccination induces antibody levels significantly higher and likely more durable compared to those produced after infection with SARS-CoV-2.