The Medical University of Vienna conducted a large-scale study of the 3rd booster vaccination in collaboration with the Arbeiter Samariter Bund Wien and the City of Vienna: Covid-BOOSTER trial
Summary
In collaboration with the Arbeiter Samariter Bund Wien and the City of Vienna, the Medical University of Vienna conducted a large-scale study of the 3rd booster vaccination in 5,000 volunteer participants. The participants were recruited at Austria's largest vaccination site, the Austria Center Vienna. In addition, all employees of the AKH Vienna were offered participation.
Three blood samples were taken. The first one directly after the booster vaccination, the second one 4 weeks after the vaccination and the third one 6 months after the vaccination.
Spike antibodies and antibodies against nucleocapsid were measured in all 3 blood samples. The latter provide information about a previous infection.
Questionnaires were used to collect data on adverse reactions to vaccination and history of infection with coronavirus.
It was shown that the 3rd vaccination is safe. Of 5,000 vaccinated participants, 5 had reported serious adverse events after 4 weeks of which 3 are suspected to be related to vaccination. (There were isolated reports of persistent side effects after vaccination such as shortness of breath, decrease in performance, sleep disturbances, impaired vision, and cardiac arrhythmias. These were difficult to record, however, because in most cases no physician visits had occurred).
There were no differences in the side effect profile between the mRNA vaccines from Biontech/Pfizer and Moderna.
Furthermore, the booster vaccination was shown to provide good protection against severe courses: Of 3759 subjects who showed up for the month 6 visit, 1372 had experienced infection after the 3rd Corona vaccination. Only 1 study subject required hospitalization, none in the intensive care unit. Furthermore, symptoms were reported as none to mild by 41% of participants. Only 10% had described their symptoms as severe.
The study was also able to show that there was a substantial new production of antibodies against the coronavirus. Antibody levels in the participants increased by an average of 16,000 BAU/ml, additionally high antibody levels were associated with better protection against corona infection.
Results of the particular examinations
Baseline
In the first examination, those participants who received the AstraZeneca vaccine for baseline immunization had the lowest average antibody level (392.7 BAU/mL), while those who received the BioNTech/Pfizer vaccine had an average level of 1179.5 BAU/mL. The highest average level was achieved by those participants who received the Moderna vaccine (2098.2 BAU/mL). It was noticeable that in the BioNTech/Pfizer group, higher age of the person was associated with significantly lower antibody levels (per year on average -21.5 BAU/mL).
Depending on the vaccine, different factors were identified for higher antibody levels at baseline immunization. Participants with systemic side effects (e.g. fever, joint pain, headache...) and smokers had higher levels (BioNTech/Pfizer). A longer interval between first and second vaccination (BioNTech/Pfizer and AstraZeneca) and absence of preexisting conditions (all vaccines) were also associated with higher levels.
Week 4
Booster vaccination with Moderna increased antibody levels more than BioNTech/Pfizer (37,707 vs. 27,176 BAU/mL).
Those participants who had only local side effects (redness, swelling, or pain at the injection site) had a lower antibody increase than those with systemic side effects (e.g., fever, joint pain, headache...). The use of NSAIDs (non-steroidal anti-inflammatory drugs such as ibuprofen, diclofenac...) had no effect on the number of antibodies formed.
Additional determination of neutralizing antibodies was performed in a part of the study participants (1060 subjects). The neutralization of the wild type and the omicron variant was determined. It was shown that a high number of total antibodies also means a high amount of neutralizing antibodies. The probability of reaching the expected threshold corresponding to sufficient neutralization against the wild type was greater than 90% for all vaccination strategies. However, this threshold for neutralization against the omicron variant was reached only in 50% of cases when vaccinated with Moderna or more than one type of vaccine. If BioNTech/Pfizer was administered for all three vaccinations, the probability was even lower.
Six months
At the final visit, the focus was on breakthrough infections; these were defined as infection after the 2nd visit (equivalent to four weeks after booster vaccination). Slightly more than one third (36%) of the participants had such a breakthrough infection.
Those participants who did not experience a breakthrough infection had higher average antibody levels at both the first and second visits (week 0 and week 4). This may indicate an association between high antibody titers and decreased infection rates.
In the course of the last visit, blood groups were additionally queried, however, no effects of blood group on antibody levels or infection probability could be determined by means of our analyses.
((Influenza
A substudy captured the differences in immune response to Covid 19 vaccination and influenza vaccination when given separately or in combination. This study arm was conducted in healthcare workers. Antibody levels to Covid and/or immunity to four different influenza virus strains were tested.
Adverse events were equally common in the combined group as when Pfizer-BioNTech was given alone; influenza vaccination alone resulted in a lower likelihood of side effects.
There are no objections to combined vaccination on safety grounds, but the effectiveness of the Covid vaccine is reduced with combined administration because fewer antibodies are produced against the coronavirus.))