3rd COVID-19 Vaccine Seen to ‘Strongly’ Raise Patients’ Immunity

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A third COVID-19 vaccine dose boosts immune responses against the SARS-CoV-2 virus in people with ANCA-associated vasculitis (AAV), researchers in Germany report.

Antibodies against the virus and the ability to fight off more highly transmissible variants like delta dip over time after the second dose. But they rise again — and more strongly than before — after the third shot in most patients, the researchers noted.

However, people taking rituximab, an immunomodulatory treatment for AAV, had lower immune responses and less protection against the delta variant than others.

The report, “Third COVID-19 vaccine dose with BNT162b2 in patients with ANCA-associated vasculitis,” was published as a letter in Annals of the Rheumatic Diseases

 AAV patients often take immunosuppressive treatments to manage the disease. But dampening the immune system can make a person more susceptible to severe COVID-19 infection, and it could inhibit the body’s ability to create antibodies against the virus after infection or vaccination.

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Previous research showed that immune responses after the standard two dose regimen of COVID-19 vaccines were subdued in immunocompromised AAV patients.

In light of this vulnerability, new COVID-19 variants that easily spread from person to person — like the delta variant (omnicron, the most transmissible variant to date, is not mentioned in this report) — may be of particular concern for these patients. A booster of the vaccine could improve its long-term efficacy and provide more protection against these concerning variants for people with autoimmune conditions like AAV.

To examine the effects of a third dose on vaccine-induced immune responses, researchers conducted an observational study of 21 AAV patients across three German vasculitis centers. All patients were on standard immunosuppressive treatments for AAV, and all received three doses of the Pfizer-BioNTech COVID-19 vaccine.

Patients’ median age was 71, and seven were female (33%).

The researchers tested for the presence of antibodies against the virus at three time points: between 21 and 58 days after a second vaccination, immediately before dose three, and 21 days (three weeks) after that third booster dose.

Antibodies against the virus’ spike S1 protein were measured and expressed as an antibody index. A higher index indicates more antibodies, or a greater immune response.

After the second vaccine dose, the median antibody index was 1.6, which fell to 0.1 just before dose three, a median of 103 days after the second shot, results showed. This drop indicated a decrease in antibodies over those roughly 3.4 months.

Once the third dose was administered, the median index jumped to 5.6, a significantly greater response than that observed after two doses.

Another test, called the surrogate virus neutralizing assay, was used to determine how well each patient’s antibodies could stop the virus from binding to and entering cells. A higher percent of virus inhibition suggests more virus-neutralizing antibodies are present.

Here, similar trends were observed. The median virus inhibition was 34% after dose two and 9% just before dose three, then rose to 56% after dose three, again indicating an improved immune response with the third vaccine.

Subsequent analyses showed that the ability to fight off the delta variant was also boosted by the third dose. The researchers tested this in vitro [lab experiment], where cells were infected with the delta variant and then exposed to the patients’ blood serum, which contained the antibodies they had produced against the virus. Virus levels after exposure to these antibodies were measured.

Serum from six out of 16 patients (38%) had some neutralizing, or inhibitory, activity against the delta variant after the two-dose regimen. Just before the third injection, three patients (13%) showed some such activity.

Many patients with measurable antibody levels in the previous two assays did not show an ability to neutralize delta, the researchers pointed out.

“Even patients with detectable antibodies in commercially available anti-S1 IgG or surrogate neutralising assays had no neutralisation against [delta],” they wrote.

After a third dose, the number of patients with neutralizing activity against delta increased to twelve (57%).

Immune responses to the vaccine, however, were significantly suppressed in patients being treated with rituximab (sold as Rituxan among other brand names), the researchers noted. This finding has also been observed in previous studies.

These patients had fewer antibodies overall, even after the third dose. While 12 out of 13 patients (92%) not on rituximab had neutralizing activity against delta, no patient using rituximab showed neutralizing activity.

“A third vaccine dose with BNT162b2 [Pfizer-BioNTech COVID-19 vaccine] induced a strong neutralising antibody activity against [delta] in most individuals; however, patients receiving rituximab maintenance therapy showed no [antibody] vaccine response even after a third vaccine dose,” the researchers wrote.

The third dose was reasonably well tolerated, with adverse reactions at the injection site being more frequent after the third dose compared with the first two doses, but systemic reactions were rare. No patients experienced a disease flare after vaccination.

“Consistent with other studies on the immunogenicity of COVID-19 mRNA vaccines in immunosuppressed patients with autoimmune diseases, our data indicate that most individuals have detectable antibody levels in commercially available assays after standard two-dose vaccination, but at significantly lower levels as compared with healthy individuals,” the researchers wrote.

“Summarised, this study suggests that immunosuppressed patients with AAV may not be adequately protected against [delta] after standard two-dose COVID-19 vaccination,” but “a third vaccine dose … induced a strong neutralising antibody activity against [delta] in most individuals,” the team concluded.