Herd immunity through vaccination is essential in ending the pandemic. Vaccines would help to reduce COVID-19 transmission and the risk of dying by boosting our immune system. However, data on mRNA vaccines and their effect on early humoral immune responses remain limited.
A new study published ahead of print in the Clinical Chemistry and Laboratory Medicine (CCLM) journal reports the production of a robust immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the Pfizer-BioNTech BNT162b2 vaccine. The increase in humoral immunity includes elevated Immunoglobulin G (IgG) and Immunoglobulin A (IgA) levels after the second mRNA dose.
The researchers write:
“Monitoring anti-SARS-CoV-2 neutralizing antibodies (especially IgG and IgA) will help in defining whether additional strategies shall be envisaged, such as modifying the current vaccine formulations or revolutionizing administration plans, entailing for example the administration of additional vaccine boost(s) for enhancing neutralizing antibodies for achieving protective titer against new SARS-CoV-2 variants displaying potential for immune escape.”
How they did it
The research team conducted a three-case series involving two females, one 44 and another 39 years old, and one 53-year old male. All three were healthcare workers who received their first Pfizer vaccine dose in Italy on January 7, 2021, followed by a second dose 21 days later.
Blood samples were collected after the first dose and then repeatedly between the first and second dose — days 1, 4, 7, 11, 14, 21 and 2 hours before vaccination. Blood samples were also taken several days after vaccination up to 63 days after.
“Specifically, we applied a narrow sequence of blood sampling, which allowed for (i) early identification and strict monitoring for the emergence and progression of anti-SARS-CoV-2 antibodies, (ii) assessment of humoral response with measurement of all relevant antibody classes (i.e., total Ig, IgM, IgA and IgG), and (iii) monitoring of serum concentration of SARS-CoV-2 spike protein, eventually produced after vaccination.”
The sampling allowed researchers to evaluate total Ig anti-RBD levels, anti-S1/S2, and anti-RBD IgG levels.
Nasal swabs were also collected three days before vaccination to evaluate the presence of SARS-CoV-2 RNA.
Increasing antibody production after the first Pfizer dose
There was no significant side effect associated with SARS-CoV-2 infection, with all patients commonly reporting localized pain at the injection site for 8 to 36 hours.
None of the subjects were positive for COVID-19 infection and were considered seronegative. However, they began to be seropositive 7 to 11 days after vaccination.
Total anti-RBD Ig, the S1/S2, and anti-RBD IgG increased 91 and 368 folds from day 11. The gradual increases persisted up to 21 days after the first dose, where the researchers then observed a plateaued response.
IgA levels targeting the spike S1 protein were elevated 7 to 11 days after the first dose. Although, the researchers observed a ‘smooth decline’ between days 14 and 21.
Immune response following second Pfizer dose
There was approximately a 30-fold increase in total Ig anti-RBD and an approximately 8-fold increase for antibodies specific to S1/S2 and anti-RBD IgG after the second vaccine. The peak of immune response occurred 35 days from when the first dose was administered — consistent with people gaining full immunity two weeks after the second shot.
Afterward, antibody levels showed a marginal decrease with a second plateau 50 days after the first vaccine dose. However, antibody levels continued to be higher after the second dose compared to after the first dose.
The second shot gave approximately a 1.3-fold boost in anti-S1 IgA levels with a peak at day 28 that was 4- to 7-fold higher than before vaccination. While IgA levels gradually declined after the peak, levels continued to be 15-fold higher than before vaccination.
Results showed a significant correlation between increases in total Ig anti-RBD levels, anti-S1/S2, and anti-RBD IgG. There were also significant correlations with other antibodies targeting SARS-CoV-2 but at a lower rate.
Given the safety and efficacy of coronavirus vaccines such as Pfizer, the study authors conclude having a sustained immune response with high neutralizing antibody titers will be essential for protection against SARS-CoV-2 and its variants of concern.
- Danese, Elisa, Montagnana, Martina, Salvagno, Gian Luca, Peserico, Denise, Pighi, Laura, De Nitto, Simone, Henry, Brandon M., Porru, Stefano and Lippi, Giuseppe. "Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series" Clinical Chemistry and Laboratory Medicine (CCLM), vol. , no. , 2021. https://doi.org/10.1515/cclm-2021-0339, https://www.degruyter.com/document/doi/10.1515/cclm-2021-0339/html