How do immunocompromised patients respond to COVID-19 vaccines?

COVID-19 vaccines produce increased antibody activity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, new research suggests that not all vaccine responses are created equal. Their results showed that immunocompromised patients, such as transplant recipients, without prior exposure to SARS-CoV-2 produced little or no neutralizing antibodies.

The researchers write:

“Consistent with other researchers’ findings, we show that COVID-19 naïve heart and lung transplant recipients have a profound reduction in neutralizing antibodies against the SARS-CoV-2 spike protein and levels of specific immunoglobulins. receptor binding domain after the priming and booster assay vaccine. However, transplant recipients who had COVID-19 infection prior to vaccination had SARS CoV-2 neutralizing antibodies at baseline which increased after vaccination. “

The study “Vaccine serological responses in transplant patients are associated with infection with COVID-19 and peripheral T-helper cells” is published and available on the website medRxiv* preprint server.

Transplant recipients had lower antibody levels after vaccination

The researchers measured the antibody responses induced by the vaccine in patients who received heart and lung transplants. They compared the effectiveness of the antibody levels of these patients against several variants of concerns. Finally, they profiled the adaptive immune response of patients, including CD4 + 74 T helper cells, CD8 + T cells, and B cells.

Vaccinated heart and lung transplant recipients without a history of COVID-19 infection had lower IgG levels that would recognize and target the SARS-CoV-2 receptor binding domain than non-immunocompromised people.

Antibody levels in vaccinated transplant patients were 22 times lower after eight days of receiving the second COVID-19 vaccine. After 30 days of the second dose, IgG levels were 20 times lower than those considered healthy and vaccinated.

Decreased neutralizing activity against SARS-CoV-2

Similar to their IgG levels, transplant recipients also showed decreased activity of neutralizing antibodies against SARS-CoV-2.

Eight days after receiving the second vaccine, transplant recipients had 12.2 times less neutralizing activity than healthy controls. Thirty days after the second dose, neutralization was 12 times less than that of healthy controls.

Transplant recipients also exhibited weaker neutralization against the worrisome variants of the E484K / N501Y / D614G mutations such as the beta (B.1.351) and gamma (P.1) variants.

Whether it was before or weeks after the second dose, the neutralization against these variants was 22% lower than the neutralization of the D614G variant. Against a virus similar to the Alpha variant (B.1.1.7) with the N501Y / D614G mutation, there was a 24% neutralization. However, the researchers note that the differences in neutralization between D614G and N501Y / D614G were not significant.

Transplant recipients and healthy controls have strongly correlated IgG antibody levels targeting the SARS-CoV-2 receptor binding domain and neutralizing antibody titers. However, this correlation was reduced when mutations were added to the mix.

Antibody response increased over time in transplant recipients

Transplant recipients took longer than healthy controls to show an increase in IgG antibody levels 20 days after their first dose of vaccine. After the second dose of vaccine, IgG levels and neutralizing activity gradually increased in two transplant recipients and the rest of the healthy controls. Increased neutralizing activity was associated with increased IgG levels. However, this simultaneous increase in IgG levels took longer in transplant recipients than in healthy controls.

Three transplant recipients had previously recovered from COVID-19 infection before being vaccinated. However, one of them had been infected between the first and second doses of the vaccine.

Of the 4 transplant recipients, 3 showed IgG levels and antibody neutralization activity comparable to healthy controls. Once vaccinated, there was an increase in IgG levels and neutralizing activity.

Overall, transplant recipients who showed a vaccine response differed from vaccinated transplant recipients who had previously been infected with COVID-19.

“The proximity to the transplant and the higher doses of immunosuppressive drugs typically given around the transplant may have contributed to the lack of response in the non-responder infected with COVID-19, as this individual developed less infection. one year after transplant, while the other three COVID-19 transplant recipients infected with -19 developed infection 2-5 years and> 15 years after transplant, ”the researchers explained.

Immune response

Transplant recipients showed significant differences between CD3 + lymphocytes, CD4 + T lymphocytes, peripheral helper T cells, Tregs and DR + T cells.

There were reduced TPH / CD4 + and DR + / CD4 + cells in transplant patients than in healthy controls.

Peripheral helper T cells showed the strongest correlation with the antibody response.

“Overall, the disparate humoral immune response to SARS-CoV-2 vaccine compared to natural infection in heart and lung transplant patients suggests vaccine failure to induce immunosurfacing in highly immunosuppressed patients.” , and underlines the need for an alternative vaccines for these populations ”, concluded the researchers.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.