Entering the third year of COVID-19 pandemic and registering in Romania already over 2,6 million cases 1 with over 62,000 deaths 2 the vaccination route of the population reached just a 36% percentage of the total population. As COVID-19 will enter its endemic phase, prevention and control raise severe challenges. In the third year of COVID-19 we still have no specific treatment, therefore promoting vaccinations and developing herd immunity are the only effective and economic measures to control the current pandemic 3.
Extended studies that focus on the antibody levels triggered by infection and/or by vaccination have reported the existance of an entire panel of specific immunoglobulines 4. Moreover, recent studies show that cross immunity against coronaviruses can be elicited by vaccination 5 but still we have to focus on the relevance of the booster vaccination.
Within the total population, healthcare workers (HCW) represent the highly exposed populational segment. Therefore, monitoring HCW characteristics and response to vaccination represents a good overall example of vaccine efficacy. Moreover evaluating vaccine efficacy against SARS-CoV-2 variants is seminal to sustain proper information to the large population and to guide public health in this pandemic 6. A recent finding suggests that the mRNA vaccine booster, associates with a good protection against Omicron and Delta variants when comparing the effect to unvaccinated or to the two doses vaccination 7. In an Italian cohort comprising almost one year of follow-up and over 33 million tested subjects important issues emerged. When epidemic phase registered Delta variant circulation vaccine effectiveness decreased from 82% to 33% at 7 months after the second dose. Moreover the study showed that high risk individuals aged ≥80 years after 7 months seemed not to be protected after the second dose of vaccine. Therefore, the authors sustain a booster vaccination even earlier than six months after the primary vaccination cycle 8. The Israeli reports done on immunity wanning and booster reccomandation are numerous. Thus, in August 2021, in Israeli HCW, the surge of SARS-CoV-2 infections, mostly by Delta variant, appeared in 21.4% individuals that received only the two dose regimen while the rate in the HCW group that have received a booster was only 0.7%. Therefore, in this group, a booster vaccination indicates substantial protection by a third vaccine dose 9 while previous studies in the same country have shown that at 3 months most HCWs still had measurable antibodies 10. Nevertheless in the same country at 5 months, a third dose of the BNT162b2 mRNA vaccine is effective in protecting subjects against severe COVID-19, compared with the subjects receiving only two doses11. Additionally, half a year after first vaccination with the BNT162b2 vaccine second dose, the humoral response was found substantially decreased, more specifically in men, over 65 years of age or older, and among immunosuppressed subjects12.
When examinating total and neutralizing antibodies raised in HCW against SARS-CoV-2 Spike protein, from Washington-1 (WA-1), Beta, Delta and Omicron variants of concern it was shown that mRNA booster eliminates the immune escape phenomena observed with the Omicron variant after two-dose vaccination 13. Another study has shown that although neutralizing antibodies raised by two-dose vaccination decreased 5 months after the second vaccination, specific T and B lymphocytes were still detectable, and upon 3rd dose induced a quick recall response. An interesting finding of the study showed that although HCWs with low antibodies response to two doses prooved good specific immune memory, that was quickly recalled by the third dose14. In over 3,000 HCW subjects from an Italian hospital, infection after vaccination occurred in 0.5% subjects mostly asymptomatic with no predominance of a specific viral variant15. Somewhat similar results were obtained in a Turkish HCW cohort were 4.5% of vaccinated personel were infected with SARS-CoV-2 16 and the booster dose of CoronaVac was advised17.
Combination of vaccination has shown that combining mRNA-mRNA or vector-mRNA types induces high neutralization titers against SARS-CoV-2 18. Another combination study done in Spanish HCW has reported results for the combination of one dose of ChAdOx1-S-nCoV-19 followed by a second dose of the Pfizer BNT162b2 vaccine as a booster. The heterologous vaccinated subjects proved a stronger neutralizing activity no matter of the SARS-CoV-2 variant. The enhanced neutralizing potential is due to the appereance of switched and activated memory B cells 19. A study published almost concomitantly with the later one, has shown that T cell activation markers increase after vaccination. Plasma from previously infected subjects or 3 dose vaccinated subjects had a better neutralization capacity compared to the plasma harvested from non-infected individuals receiving two vaccine doses 20.
In CoronaVac vaccination it was shown that after 6 months post-vaccination almost all HCW subjects has prooved a decreased antibody persistance21. AZD1222 (ChAdOx1) vaccination study has shown also an important decline in antibody levels in HCW, months after vaccination22. In a Correan HCW BNT162b2 vaccinated cohort it was shown that after six months, serum antibody levels significantly declined 23. In Finland, mRNA vaccine displayed only 53% from the initial IgG level after 6 months, but antibody waning was not observed against COVID-19 hospitalization24. In a HCW Polish cohort it was reported that there are higher levels of specific antibodies 6 months after vaccination in subjects experiencing the disease after the first round of vaccination, the finding supporting once more the use of a booster dose, especially for non-infected subjects25.
In Indonesian HCW specific IgG persisted 3 months post-vaccination with an inactivated SARS-CoV-2 vaccine. The authors point out that there is an increased decline of the specific antibodies in subjects without prior SARS-CoV-2 infection, finding that sustains the need for an additional booster dose26.
IgA is an antibody that sustains the humoral mucosal immunity especially in viral respiratory infections, and that there are few studies that evaluate the circulatory form of the antibody in COVID-1927,28. We have previously shown that post-vaccination, specific serum IgA is triggered in similar levels with IgG and having the same antibody dynamics 29, while other studies have reported saliva IgA in low levels upon vaccination 30. At 6 months, post-vaccination specific IgA serum levels showed a significant descending trend 31. In a Dutch cohort vaccination with several vaccine types (mRNA-1273, BNT162b2, Ad26.CoV2-S or ChAdOx1-S) was studied and the authors point out that specific T cell responses were detectable one year post-vaccination while the humoral responses retained up to four months32.
Immune response wanning upon vaccination in COVID-19 is an important issue in the current pandemics, mostly in HCW. Therefore, our study aimed to establish the specific humoral response of antibodies IgG and IgA, upon specific vaccination, during the second year of pandemia and evaluating the booster shot with the same vaccine type and dose.