Antibodies spiked then waned after Pfizer, Moderna COVID vaccines, but J&J response was opposite

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In a head-to-head comparison today in Scientific Reports, University of California San Francisco (UCSF) researchers describe very different antibody responses to the monovalent (single-strain) Pfizer/BioNTech, Moderna, and Johnson & Johnson (J&J) COVID-19 vaccines up to 6 months after receipt.

In the observational study, the researchers compared the neutralizing antibody (nAB) responses of 498 healthy volunteers aged 18 to 88 years given the Pfizer (287 people) or Moderna (149) mRNA vaccines, or the J&J (62) adenovirus-vector vaccine in spring 2021. Participants gave blood samples for measurement of nABs and completed questionnaires before vaccination and 1 and 6 months after completion of the primary vaccine series.

The researchers did not assess vaccine effectiveness, or how well the vaccines protected the recipients from COVID-19 and severe outcomes. Scientists look for a robust immune response—measured by how many antibodies the body produces—as a hopeful sign, given that antibodies help fight disease.

J&J outpaces Pfizer at 6 months

One month after COVID-19 vaccination, compared with J&J recipients, nAB levels were 51 times higher among Moderna recipients and 21 times higher among Pfizer recipients. At 6 months, however, J&J vaccinees produced the same antibody response as that of Moderna and significantly higher concentrations than those of Pfizer.

Specifically, 99.3% of Pfizer, 99.3% of Moderna, and 59.7% of J&J recipients had measurable nABs at 1 month. By 6 months, 92.2% of Pfizer, 97.9% of Moderna, and 89.5% of J&J vaccinees had nABs.

During the same period, concentrations fell among Pfizer (-0.16 fold; average difference, -0.79; 95% confidence interval [CI], -0.85 to -0.73) and Moderna (-0.18 fold; average difference, -0.75; 95% CI, -0.84 to -0.67) vaccinees, while nABs in J&J recipients rose significantly (5.8-fold; average difference, 0.76; 95% CI, 0.63 to 0.90).

"This was the most striking finding," lead author Aric Prather, PhD, said in a UCSF press release. "While the mechanism for this increase is unknown, other smaller studies have suggested this trend, leading us to believe there are robust phenomena not specific to our sample."

Huge impact of smoking

Older age was tied to lower neutralizing antibody levels for Pfizer (-17%) and J&J (-11%) vaccine recipients but not for those given the Moderna vaccine. A higher baseline body mass index (BMI) was linked to lower antibody concentrations in J&J recipients (-11%) but not in Pfizer or Moderna vaccinees. Women and nonsmokers had higher nAB levels than men (-30%) and smokers (-240%), respectively.

"It is encouraging that the stronger vaccine, Moderna, mitigated the effects of some risk factors, particularly age," senior author Elissa Epel, PhD, said in the release.

Detectable baseline concentrations of anti-spike antibodies, indicative of previous infection, were associated with higher post-vaccination nABs for each combination of vaccine and time point except for the J&J vaccine at 6 months.

It is encouraging that the stronger vaccine, Moderna, mitigated the effects of some risk factors, particularly age.

Elissa Epel, PhD

While the three vaccines have been replaced by the updated bivalent (two-strain) mRNA COVID-19 vaccines from Pfizer and Moderna that target both the wild-type virus and the Omicron BA.4 and BA.5 subvariants, the researchers said the identified risk factors may also apply to the updated vaccines.

"While we have not studied the bivalent vaccination specifically, it's likely that factors like older age, male sex, smoking status and higher BMI can prevent optimal antibody response to the vaccine," Epel said.

The researchers plan to next compare nAB responses to the bivalent Pfizer and Moderna COVID-19 vaccines. "As more studies are carried out, comparing adenovirus vector-based vaccines and mRNA-based vaccines, these findings may help inform when and for whom vaccine boosters are indicated," they wrote.