A recent study published within the journal Scientific Reports evaluated the sturdiness of neutralizing antibody (nAb) responses induced after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

The Food and Drug Administration (FDA) authorized two messenger ribonucleic acid (mRNA)-based vaccines (BNT162b2 and mRNA-1273) and one adenovirus vector-based vaccine (Ad26.COV2.S) for emergency use for defense against SARS-CoV-2. While these vaccines confer significant protection against severe coronavirus disease 2019 (COVID-19), increasing evidence suggests a waning of protection over time. As well as, studies have identified several predictors of nAb responses to vaccination. Nonetheless, less is understood in regards to the durability of nAb responses by vaccine type.

Predictors of long-term neutralizing antibody titers following COVID-19 vaccination by three vaccine types: the BOOST study. ​​​​​​​Image Credit: Shutterstock

The study and findings

In the current study, researchers investigated and compared the sturdiness of nAbs elicited by BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines. Non-vaccinated healthy adults were recruited between March 6 and April 17, 2021, within the constructing optimal antibodies study (BOOST), an observational study, to discover predictors of the immune response to the SARS-CoV-2 vaccine series.

Participants were eligible in the event that they were 18 or older, non-vaccinated, and willing to finish questionnaires and supply blood samples at baseline, one month, and 6 months after the last vaccine dose. Subjects were excluded in the event that they were pregnant, receiving cancer treatment, taking medicines that affect the immune system, or had a history of immune-related diseases. Nonetheless, participants weren’t excluded in the event that they had a previous history of COVID-19.

Sociodemographic and behavioral aspects, including age, sex, and smoking status, were self-reported by participants. Serum nAbs against SARS-CoV-2 were assessed using high-throughput pseudovirus neutralization assays. Anti-spike protein antibodies were quantified at baseline by enzyme-linked immunosorbent assay (ELISA). Anti-nucleocapsid antibodies were measured at one and 6 months. A linear mixed-effects model was fitted to log-transformed neutralization data.

Findings

The team recruited 534 participants; the ultimate analytic sample comprised 498 subjects. Participant characteristics, except age, weren’t different by vaccine type. Ad26.COV2.S recipients were barely older than others. Each vaccine generally increased neutralization at one and 6 months. Specifically, around 95% of participants showed nAbs at one month – 99.3% of BNT162b2, 99.3% of mRNA-1273 recipients, and 59.7% of Ad26.COV2.S recipients.

nAbs declined over time amongst those vaccinated with BNT162b2 or mRNA-1273 but increased amongst Ad26.COV2.S recipients. On the six-month follow-up, 93.5% of subjects had nAbs, including 97.9% of mRNA-1273, and 89.5% of Ad26.COV2.S, and 92.2% of BNT162b2 recipients. nAbs were 51- and 21-fold higher at one month amongst BNT162b2 and mRNA-1273 recipients, respectively, than Ad26.COV2.S vaccinees.

Participants vaccinated with the mRNA-1273 vaccine had 1.7-fold higher nAbs than those that received the BNT162b2 vaccine. At six months, Ad26.COV2.S vaccinees had higher 1.7-fold higher nAb responses than BNT162b2 recipients and 0.63-fold reduced nAbs than mRNA-1273 recipients. Consistently, mRNA-1273 recipients sustained (2.7-fold) higher nAb responses than BNT162b2 vaccinees at six months.

Sensitivity analyses restricted to SARS-CoV-2 infection-naïve participants (93% of the cohort) had similar findings. The authors identified several individual-level aspects that predicated nAb durability over the six-month follow-up. Advanced age was related to lower nAbs for BNT162b2 or Ad26.COV2.S recipients but not for those vaccinated with the mRNA-1273 vaccine, independent of the follow-up time point.

Increased baseline body mass index (BMI) was related to lower nAb responses for people vaccinated with Ad26.COV2.S, but not for mRNA-1273 or BNT162b2 vaccinees. Females showed 1.3-fold increased nAb responses relative to males, no matter time point or vaccine type. Furthermore, non-smokers exhibited higher nAb responses than smokers. Anti-spike antibodies at baseline, suggestive of prior infection, were related to increased nAbs post-vaccination, aside from Ad26.COV2.S recipients at six months.

Conclusions

The researchers observed that mRNA vaccines initially elicited higher nAb responses than the adenovirus-vectored vaccine. Nonetheless, nAbs significantly declined in mRNA vaccine recipients over six months. Contrastingly, there was a big 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 those vaccinated with the BNT162b2 vaccine.

mRNA-1273 recipients showed higher nAbs than BNT162b2 vaccinees and weren’t significantly different from those vaccinated with the Ad26.COV2.S vaccine. The authors also identified several aspects related to nAb durability. For instance, smoking or being male was related to lower nAbs whatever the vaccine type. As well as, the consequences of BMI and age differed by the form of vaccine.

The study’s limitations include the observational design and never randomizing participants to vaccine types. Besides, the neutralization assay was specific to the SARS-CoV-2 Wuhan strain. As such, nAbs against other variants couldn’t be investigated. Taken together, the findings suggest that mRNA vaccines elicit robust initial nAb responses that decline with time. In contrast, despite being lower initially, the adenovirus-vectored vaccine-induced nAb responses catch up over time.