A recent study published in the journal Scientific reports Durability was evaluated neutralizing antibody (nAb) induced responses after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The Food and Drug Administration (FDA) has authorized two ribonucleic acid (mRNA)-based vaccines (BNT162b2 and mRNA-1273) and one adenoviral vector-based vaccine (Ad26.COV2.S) for emergency use to protect against SARS-CoV-2. While these are available Vaccines provide significant protection against severe coronavirus disease 2019 (COVID-19), and mounting evidence suggests protection wanes over time. In addition, studies have identified several predictors of nAb responses to vaccination. However, little is known about the robustness of nAb responses by vaccine type.
Predictors of long-term neutralizing antibody titers after COVID-19 vaccination with three types of vaccines: the BOOST study.. Image credit: Shutterstock
Study and results
In this study, the authors examined and compared the robustness of nAbs obtained with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines. Healthy, unvaccinated adults between March 6 and April 17, 2021, were recruited into the Optimal Antibody Building Study (BOOST), an observational study, to identify predictors of immune response to the SARS-CoV-2 vaccine series.
Participants were eligible if they were 18 years of age or older, unvaccinated, and willing to complete questionnaires and provide blood samples at baseline, one and six months after the last vaccine dose. Subjects were excluded if they were pregnant, receiving treatment for cancer, taking medications that affect the immune system, or had a history of immune-related diseases. However, participants were not excluded if they had a previous history of COVID-19.
Sociodemographic and behavioral factors, including age, gender and smoking status, were reported by the participants. Serum nAbs against SARS-CoV-2 were evaluated using high-throughput liar Neutralization assays. The anti-rising protein antibody was quantified at baseline by enzyme-linked immunosorbent assay (ELISA). Nucleocapsid antibodies were measured at one and six months. A linear mixed effects model was fitted to log-transformed break-even data.
The team recruited 534 participants. The final analytical sample consisted of 498 subjects. Participant characteristics, except for age, were not different by type of vaccine. Ad26.COV2.S recipients were slightly older than the others. Each vaccine generally increased its neutralization rate at one and six months. Specifically, about 95% of the participants showed nAbs at 1 month—99.3% of BNT162b2 recipients, 99.3% of mRNA-1273 recipients, and 59.7% of Ad26.COV2.S recipients.
nAbs decreased over time among those vaccinated with BNT162b2 or mRNA-1273 but increased among Ad26.COV2.S recipients. At the six-month follow-up, 93.5% of subjects had nAbs, including 97.9% of mRNA-1273 recipients, 89.5% of Ad26.COV2.S recipients, and 92.2% of BNT162b2 recipients. nAbs were 51- and 21-fold higher at 1 month among recipients of BNT162b2 and mRNA-1273, respectively, than from Ad26.COV2.S vaccines.
Participants vaccinated with the mRNA-1273 vaccine had 1.7 times more nAbs than those who received the BNT162b2 vaccine. At six months, Ad26.COV2.S vaccines had 1.7-fold higher nAb responses from BNT162b2 recipients and 0.63-fold reduced nAb responses from mRNA-1273 recipients. Consistently, mRNA-1273 recipients had (2.7-fold) higher nAb responses than BNT162b2 vaccines at six months.
Sensitivity analyzes restricted to participants naïve with SARS-CoV-2 infection (93% of the group) had similar results. The authors identified several factors at the individual level that predicted nAb robustness over a six-month follow-up. Advanced age was associated with decreased nAbs for BNT162b2 or Ad26.COV2.S recipients but not for those vaccinated with mRNA-1273, regardless of the follow-up time point.
An increased baseline body mass index (BMI) was associated with lower responses for individuals vaccinated with Ad26.COV2.S, but not for mRNA-1273 or BNT162b2 vaccines. Females showed 1.3-fold more unprecedented responses than males, regardless of time point or type of vaccine. Moreover, non-smokers showed higher reflexes than smokers. Anti-inflammatory antibodies at baseline, indicating previous infection, were associated with increased nAbs after vaccination, with the exception of Ad26.COV2.S recipients at six months.
The researchers noted that the mRNA vaccines initially elicited higher nAb responses than the adenovirus-targeted vaccine. However, nAbs decreased significantly in mRNA vaccine recipients over six months. In contrast, there was a significant increase in nAbs over the six-month follow-up in Ad26.COV2.S recipients. Moreover, nAb responses were higher in Ad26.COV2.S recipients than in those vaccinated with BNT162b2 vaccine.
mRNA-1273 recipients showed a higher incidence of nAbs from the BNT162b2 vaccines and did not differ significantly from those vaccinated with the Ad26.COV2.S vaccine. The authors also identified several factors associated with nAb robustness. For example, smoking or being male was associated with lower nAbs regardless of the type of vaccine. In addition, the effects of BMI and age differed depending on the type of vaccine.
Study limitations include observational design and not randomization of participants to types of vaccines. Besides, the neutralization test was specific to the Wuhan SARS-CoV-2 strain. As such, nAbs cannot be investigated against other variants. Taken together, the results indicate that mRNA vaccines elicit strong initial nAb responses that decline with time. In contrast, although initially low, nAb responses induced by adenovirus vaccine catch up with time.