Third dose of BNT162b2 improves immune response in liver transplant recipients to ancestral strain but not Omicron BA.1 and XBB

Abstract

Vaccine immunogenicity in transplant recipients can be impacted by the immunosuppressive (IS) regimens they receive. While BNT162b2 vaccination has been shown to induce an immune response in liver transplant recipients (LTRs), it remains unclear how different IS regimens may affect vaccine immunogenicity after a third BNT162b2 dose in LTRs, which is especially important given the emergence of the Omicron sublineages of SARS-CoV-2. A total of 95 LTRs receiving single and multiple IS regimens were recruited and offered three doses of BNT162b2 during the study period. Blood samples were collected on days 0, 90, and 180 after the first BNT162b2 dose. At each time point, levels of anti-spike antibodies, their neutralizing activity, and specific memory B and T cell responses were assessed. LTRs receiving single IS regimens showed an absence of poor immunogenicity, while LTRs receiving multiple IS regimens showed lower levels of spike-specific antibodies and immunological memory compared to vaccinated healthy controls after two doses of BNT162b2. With a third dose of BNT162b2, spike-specific humoral, memory B, and T cell responses in LTR significantly improved against the ancestral strain of SARS-CoV-2 and were comparable to those seen in healthy controls who received only two doses of BNT162b2. However, LTRs receiving multiple IS regimens still showed poor antibody responses against Omicron sublineages BA.1 and XBB. A third dose of BNT162b2 may be beneficial in boosting antibody, memory B, and T cell responses in LTRs receiving multiple IS regimens, especially against the ancestral Wuhan strain of SARS-CoV-2. However, due to the continued vulnerability of LTRs to presently circulating Omicron variants, antiviral treatments such as medications need to be considered to prevent severe COVID-19 in these individuals.

Keywords: B cells; BNT162b2; SARS-CoV-2; T cells; antibodies; immunosuppressives; liver transplant recipients; spike protein.

Figure 1

Comparison of humoral and cellular responses between LTRs vaccinated with two and three doses of BNT162b2 and HC vaccinated with two doses of BNT162b2. (A) Comparison of IgG responses against ancestral Wuhan strain full-length spike and (B) RBD in LTRs and HC (Median Age: LTR: 59 years, HC: 60 years) on days 0, 90, and 180 post first BNT162b2 dose. (C) Comparison of RBD-specific MBC among IgG+ Antibody Secreting Cells and (D) granzyme B-producing CD8 T cell responses in LTRs and HC on days 0, 90, and 180 post first dose of BNT162b2. *p < 0.05, **p < 0.01, ****p < 0.0001, (Mann-Whitney U-test). Data are presented as medians with interquartile range. ns, not significant.

Figure 2

Comparison of humoral and cellular responses between LTRs receiving different immunosuppressive regimens and HC vaccinated with two doses of BNT162b2. (A) Comparison of IgG responses against ancestral Wuhan strain full-length spike and (B) RBD in stratified LTRs (LTRs receiving single, double, and triple IS regimens were labeled as regimens 1, 2, and 3, respectively.) and HC (Median Age: LTR Regimen 1: 59 years, LTR Regimen 2: 60 years, LTR Regimen 3: 57 years, HC: 61 years) on day 90 post first dose of BNT162b. (C) Comparison of neutralizing antibody response against ancestral Wuhan strain spike and in stratified LTRs and HC on day 90 post first dose of BNT162b2. (D) RBD-specific MBC among IgG+ Antibody Secreting Cells and (E) granzyme B-producing CD8 T cell responses in stratified LTRs and HC on day 90 post first dose of BNT162b2. *p < 0.05, **p < 0.01, ****p < 0.0001, (Kruskal-Wallis test). Data are presented as median with interquartile range.

Figure 3

Comparison of humoral and cellular responses in LTRs receiving different immunosuppressive regimens vaccinated with a third dose of BNT162b2 and HC vaccinated with two doses of BNT162b2. (A) IgG responses against ancestral Wuhan strain full-length spike and (B) RBD in stratified LTRs on day 180 post first dose of BNT162b2 and HC on day 90 post first dose of BNT162b2. (C) The proportion of anti-RBD antibody responders and non-responders (<0.8U/mL RBD IgG) in stratified LTRs. (D) Neutralizing antibody response against ancestral Wuhan strain spike in stratified LTRs on day 180 post first dose of BNT162b2 and HC on day 90 post first dose of BNT162b2. (E) RBD-specific MBC among IgG+ Antibody Secreting Cells and (F) granzyme B-producing CD8 T cell responses in stratified LTRs on day 180 post first dose of BNT162b2 and HC on day 90 post first dose of BNT162b2. *p < 0.05, **p < 0.01, ****p < 0.0001, (Kruskal-Wallis test). Data are presented as median with interquartile range.

Figure 4

Humoral response against Omicron BA.1 and XBB in LTRs after receiving the third dose of BNT162b2. IgG responses against (A) Omicron BA.1 and (B) Omicron XBB spike in stratified LTRs receiving double and triple IS regimens before and after the third dose of BNT162b2. **p < 0.01, (Wilcoxon matched-pairs signed rank test). (C) Comparison of IgG responses against Omicron BA.1 and Omicron XBB spike between stratified LTRs receiving double and triple IS regimens on day 180 post first dose of BNT162b2 and HC on day 90 post first dose of BNT162b2. Neutralizing antibody response against (D) Omicron BA.1 and (E) Omicron XBB spike in stratified LTRs receiving double and triple IS regimens before and after the third dose of BNT162b2. *p < 0.05, **p < 0.01, (Wilcoxon matched-pairs signed-rank test). (F) Neutralizing antibody response against Omicron BA.1 and Omicron XBB spike in stratified LTRs receiving double and triple IS regimens on day 180 post first dose of BNT162b2 and HC on day 90 post first dose of BNT162b2. *p < 0.05, **p < 0.01, (Kruskal-Wallis test). Data are presented as median with interquartile range. ns, not significant.