In a recent article published on the preprint server medRxiv*, researchers conducted phase 3 evaluations of the immunogenicity of the two immunization periods of the CoronaVac coronavirus 2019 (COVID-19) vaccine among Chilean adults.
Study: Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a phase 3 randomized clinical trial. Image credit: Tero Vesalainen/Shutterstock
background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China in late December 2019, is responsible for the current COVID-19 pandemic. SARS-CoV-2 has caused more than 6.41 million deaths and 581 million cases of infection over the past 2.5 years worldwide.
Establishing vaccines to stop the spread of the SARS-CoV-2 pandemic is a global priority. The World Health Organization (WHO) has approved 10 vaccine prototypes for emergency use due to global efforts to create efficient vaccines against SARS-CoV-2. In addition, more than eight billion vaccines have been given to humans to date.
An inactivated vaccine against COVID-19, CoronaVac, has been approved by the WHO for emergency use. It showed strong immunogenicity and efficacy in studies conducted in Brazil, China, Indonesia, Chile and Turkey. In Chile and Turkey, CoronaVac was 87.5% and 83.5% effective, respectively, at preventing COVID-19-related hospitalization among healthy adults.
About the study
In the current phase 3 multicenter, controlled, randomized study, scientists analyzed the immune response induced by two vaccination periods for the whole virus-inactivated COVID-19 vaccine, CoronaVac, with two vaccine shots spaced by two (program from zero to 14). ) or four (from zero to 28) weeks among healthy Chilean adults aged 18 years or older.
The study included 2,302 subjects, 440 of whom were in the immunogenicity arm. In addition, the researchers obtained blood samples from the volunteers at different time stamps.
Samples were reported from a single site. Humoral immune responses were assessed by assessing the neutralizing capacities of circulating antibodies. For this, the researchers performed neutralization tests on surrogate viruses of the ancestral SARS-CoV-2 strain (sVNTs), conventional VNTs (cVNTs) and pseudotyped VNTs (pVNTs).
Cellular immune responses were assessed by flow cytometry and enzyme-linked immunosorbent spot (ELISPOT) assay. The team measured the expression of activation-induced markers (AIM) in T cells by flow cytometry and the number of spot-forming cells (SFCs) for interferon-γ (IFN-γ) through ELISPOT.
In addition, peripheral blood mononuclear cells (PBMC) from 88 volunteers were examined for both immunization techniques and schedules. PBMCs were individually stimulated with four megapools (MP) of peptides composed of the SARS-CoV-2 proteome to test the selective secretion of IFN-γ and AIM expression of T cells in response to SARS-CoV- 2.
Mesoscale discovery (MSD) immunoassays were used to determine antibody levels against the spike protein (S) and receptor binding domain (RBD) of SARS-CoV-2 variants of concern (VOC). to determine whether the time period of immunization had any influence. on the pattern of antibodies evoked against SARS-CoV-2 VOCs. Correlation matrices were used to assess correlations in the measured data.
results
The results of the study showed that circulating antibodies generated by CoronaVac showed enhanced neutralizing abilities against SARS-CoV-2 as measured by four different assays. Both the two-week and four-week regimens of CoronaVac had strong neutralizing capabilities. However, the four-week strategy produced a better response. The authors reported that, regardless of the age group studied, CoronaVac vaccination led to significantly higher titers of circulating neutralizing antibodies for both vaccination schedules in all periods after the first and second injection.
Surprisingly, there was no variation between the schedules in the level of antibodies against protein S and RBD four weeks after the second dose. However, reduced amplitude indices were observed for the different VOCs examined, with increasing values compared to Omicron and Beta VOCs, but reduced values compared to the other zero to 28 schedule variants. This inference suggested that a booster injection might be necessary to stimulate a more effective protective humoral immune reaction against these newly developed viral variants.
Stimulation of PBMCs using MP triggered IFN-γ secretion and AIM expression similarly for both vaccination schedules. Both immunization regimens were able to promote coordinated humoral and cellular immune responses according to correlation matrices. Thus, correlation matrices indicated strong associations between IFN-γ secretion and neutralizing antibodies.
Conclusions
Collectively, the study findings showed that strong humoral and cellular immune responses were elicited by CoronaVac immunization among Chilean adults following a zero-to-28 or zero-to-14 vaccination schedule. Interestingly, the four-week schedule of the vaccine elicited a greater humoral immune reaction than the two-week schedule.
According to the scientists, further research on the current phase 3 trial will focus on the immune reaction triggered at later periods after vaccination (i.e. six and 12 months after the first dose), CoronaVac’s ability to protect against the circulating SARS-CoV-2. variants and the ability of a third dose to elicit a powerful immune response.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.