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SARS-CoV-2 Humoral and Cellular Immune Responses of Patients With HIV After Vaccination With BNT162b2 mRNA COVID-19 Vaccine in the Tel-Aviv Medical Center
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Open Forum Infectious Diseases, 23 February 2022 pdf attached
Waning immune response is associated with a higher susceptibility to SARS-CoV-2; therefore, PWH with a CD4 count <300 cells/ μL should be prioritized for vaccine boosters.
While there were only a few patients with a CD4 count <200 cells/μL to reach a level of statistical significance (3 patients), none of them had detectable anti-RBD IgG antibodies.
Abstract>
Background
Little is known about vaccine efficacy and sustainability among people with HIV (PWH). We estimated humoral and cellular immune responses postvaccination with BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine among PWH in Tel-Aviv Medical Center.
Methods
The vaccine humoral response was evaluated by measuring immunoglobulin G (IgG) titers of antispike receptor-binding domain antibodies (anti-RBD IgG). Cellular response was assessed by stimulating donor peripheral blood mononuclear cells with pooled complete S-peptide mix.
Results
One hundred thirty-six PWH who completed 2 doses of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine were tested for anti-RBD IgG and compared with 61 vaccinated health care workers (HCWs). The antibody titers were similar between the groups (median, 118 BAU/mL for PWH and 101.4 BAU/mL for HCWs; P = .231), although the mean time from second vaccine was 4.5 months in PWH and 6.7 months in HCWs (P < .0001). Longer time from second vaccine dose was associated with decreased antibody level, as were CD4 counts <300 cells/μL compared with higher CD4 counts (25.1 BAU/mL vs 119.3 BAU/mL, respectively; P = .047). There was no difference in cellular immune response between vaccinated PWH, convalescent unvaccinated PWH, and vaccinated HCWs.
Conclusions
The humoral immune response of PWH was comparable to that of HCWs after BNT162b2 mRNA vaccination. Cellular immune response did not differ between vaccinated PWH, convalescent PWH, and vaccinated HCWs. PWH with CD4 counts <300 cells/μL (n = 9) had lower antibody titers compared with patients with counts >300 cells/μL (n = 127).
DISCUSSION
We prospectively assessed a cohort of patients who had received 2 doses of the BNT162b2 mRNA COVID-19 vaccine. Previous studies had suggested good responses to vaccines among PWH on ART with high CD4 counts and good viral control [10-14]. For example, Levy et al. reported that 98% of PWH had developed anti-RBD IgG at a median of 18 days after the second vaccine dose compared with 98.9% of HCWs. Three patients with a CD4 count <200 cells/μL were included in 1 of the studies, and all 3 developed anti-RBD IgG shortly after the second vaccine [10]. However, little is known about the sustainability of the serological response.
Our data show that the level of anti-RBD IgG did not differ among PWH compared with HCWs (median, 118 BAU/mL for HIV patients and 101.4 BAU/mL for HCWs; P = .231). However, the time since the second vaccine dose differed significantly between the groups, with a mean of 4.5 months in PWH vs 6.7 months in HCWs (P < .0001). As we showed in our study, time from the second vaccine dose was associated with lower anti-RBD IgG levels. However, multivariable linear regression analysis did not show a significant difference between the groups when controlling for time from the second vaccine dose. Our patients were younger than the group of HCWs, with more males. Most had high CD4 cell counts (mean [SD], 756 [314] cells/μL) and good viremic control. Previous studies have provided evidence that advanced age is associated with diminished immune response to the BNT162b2 mRNA vaccine [15-17], especially above the age of 65. Our HCW cohort was significantly older than the PWH cohort (49 vs 44), but still relatively young; therefore, we assumed that the age difference was not a significant factor in our study, and it was further confirmed by multivariable analysis. There is conflicting evidence regarding whether there is a gender difference in the response to the BNT162b2 mRNA vaccine. Jabal et al. did not show a difference in response between male and female HCWs in Israel [15]; however, Vassilaki et al. showed a better serological response in female HCWs in Greece [16].
It is well established that patients with HIV who have low CD4 counts may have a decreased serological response to other vaccines [6-9]. Therefore, we sought to check whether a low CD4 count is associated with diminished response. Although only 3 patients with a CD4 count <200 cells/μL were included in our study, none of them had detectable anti-RBD IgG antibodies at 3-6 months after 2 vaccine doses. In the group of 9 patients with a CD4 count <300 cells/μL (which included also those with CD4 count <200 cells/μL), the level of antibodies was significantly lower than that in the group of patients with higher CD4 counts. The mean time from the second vaccine dose was a bit shorter in PWH with a CD4 count <300 cells/μL compared with patients with higher CD4 counts, reflecting a true diminished response to vaccine in this group of patients. Another factor that was associated with lower antibody level was the time since the second vaccine dose, with decreasing levels of antibodies over time. No other factor was found to influence antibody levels. Studies published recently have shown a waning humoral immune response over time, especially among men, persons above the age of 65, and immunocompromised patients [18, 19]. Waning immune response is associated with a higher susceptibility to SARS-CoV-2; therefore, PWH with a CD4 count <300 cells/ μL should be prioritized for vaccine boosters.
A recent study by Weldemeskel et al. [12] evaluated cellular response in 12 patients with HIV 7 and 17 days after the second dose of the BNT162b2 vaccine, and the results were compared with healthy donors. There was no difference in the INFγ spot-forming units or in the stimulation index between the study and control groups. In accordance with their findings, our current results demonstrated that the cellular response after stimulation with pooled complete S-peptide mix did not differ between vaccinated PWH and vaccinated HCWs, with both groups showing comparable numbers of TNFα- and INFγ-producing CD4+ T cells. Time from the second vaccine dose to cellular immunity test was similar between the groups. However, the anti-RBD IgG levels for the PWH who recovered from SARS-CoV-2 were significantly lower than those for vaccinated PWH, regardless of CD4 counts, which were similar for both groups. A previous study of non-HIV SARS-CoV-2 convalescent individuals showed that even though there was a decline in humoral response over time, T-cell response remained robust [19]. Our study shows similar results, with comparable cellular response of convalescent and vaccinated PWH over time, even with waning anti-RBD IgG levels. It could be of great interest to perform an analysis of cellular immune response to vaccine in a population of PWH with a low CD4 count (<300 or even <200 cells/μL) to better understand vaccine efficacy in preventing SARS-CoV-2 infection and severe illness in this particular group.
The strengths of our study include the evaluation of both humoral and cellular immune responses among PWH 3-6 months after vaccination, and not after a short time frame of 1-2 weeks. We also assessed the cellular response in a larger cohort of vaccinated PWH than reported previously and compared it with both PWH who had been infected with SARS-CoV-2 and with vaccinated HCWs.
Our study has several limitations that bear mentioning. First, we performed an assessment of cellular and humoral responses during a wide time frame of 3-6 months. In addition, the group of HCWs was smaller and was not properly matched to the group of PWH in age, gender, or time from second vaccine dose. All those could influence the study results. However, multivariable analysis that controlled for age, gender, and time from second vaccine dose did not show significant differences between the groups. Second, patients with very low CD4 counts were underrepresented in our study, and evaluating the sustainability of immune response in this group of patients would have been of considerable interest. Third, our cohort was relatively healthy; only 9% of patients had hypertension, and 7% were obese. The majority of the patients were MSM. These characteristics reflect the population of PWH in Tel-Aviv, who are younger and healthier, but do not necessarily reflect the general population of PWH in Israel.
Finally, our study aimed to assess humoral and cellular immune response, and not the clinical efficacy of preventing SARS-CoV-2 infection or severe illness.
In conclusion, after vaccination, PWH showed anti-RBD IgG levels similar to those of HIV-negative HCWs. However, PWH who had a CD4 count <300 cells/μL had a decreased level of anti-RBD IgG compared with PWH with higher CD4 counts. Cellular immune response did not differ between vaccinated PWH, PWH who had recovered from SARS-CoV-2, and vaccinated HCWs. However, anti-RBD IgG was higher in vaccinated PWH compared with PWH who had recovered from COVID-19 infection.
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