Humoral and cellular immune response and the safety of third SARS-CoV-2 mRNA vaccine with longer interval after the second vaccination in kidney transplant recipients

Takai, Satoshi; Nishida, Hayato; Ito, Hiromi; Fukuhara, Hiroki; Nawano, Takaaki; Narisawa, Takafumi; Kanno, Hidenori; Yagi, Mayu; Yamagishi, Atsushi; Sakurai, Toshihiko; Naito, Sei; Kato, Tomoyuki; Morikane, Keita; Tsuchiya, Norihiko

doi:10.3389/fimmu.2022.1050211

Cited by 9 publications

(6 citation statements)

References 31 publications

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“…These evidences supported the antibody responses in the longer interval group was better than those in the shorter interval group. The above data confirmed that an appropriate length of interval between COVID-19 vaccine doses should be part of an effective vaccination protocol (41). An optimal inoculation interval would reduce inoculation frequency and therefore limit costs, which is particularly important in the resource-poor areas with a shortage of vaccine supply.…”

Section: Discussionsupporting

confidence: 63%

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV

Wang

Zhang

et al. 2023

Front. Immunol.

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IntroductionVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals.MethodsA total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis.ResultsAt 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron.DiscussionThis study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

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Section: Discussionsupporting

confidence: 63%

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV

Wang

Zhang

et al. 2023

Front. Immunol.

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“…The booster shot induced production of nAbs against the ancestral SARS-CoV-2 strain also in primary non-responder KTR subjects [ 13 , 14 , 15 ], although some of the recipients did not mount a detectable humoral immune response following the 3rd dose [ 16 ], while nAb titers were lower against Alpha, Beta, Delta and Omicron variants in both KTR and the general population [ 17 , 18 ], as confirmed by pseudotyped lentivirus [ 19 ] and live virus-based tests [ 20 ]. Moreover, the role of T cells in conferring protection has been underlined [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies investigated the cellular immune response in KTR assessing spike-specific IFN-γ production by ELISPOT assay [ 21 , 25 ] or ELISA quantization [ 26 , 27 ]. Here, we evaluated humoral and cellular immune responses in a small cohort of KTR and healthy individuals after the 2nd and 3rd dose of BNT162b2 Pfizer-BioNTech vaccine.…”

Section: Introductionmentioning

confidence: 99%

Booster Dose of SARS-CoV-2 mRNA Vaccine in Kidney Transplanted Patients Induces Wuhan-Hu-1 Specific Neutralizing Antibodies and T Cell Activation but Lower Response against Omicron Variant

Del Mastro,

Picascia,

D’Apice

et al. 2023

Viruses

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Kidney transplanted recipients (KTR) are at high risk of severe SARS-CoV-2 infection due to immunosuppressive therapy. Although several studies reported antibody production in KTR after vaccination, data related to immunity to the Omicron (B.1.1.529) variant are sparse. Herein, we analyzed anti-SARS-CoV-2 immune response in seven KTR and eight healthy controls after the second and third dose of the mRNA vaccine (BNT162b2). A significant increase in neutralizing antibody (nAb) titers were detected against pseudoviruses expressing the Wuhan-Hu-1 spike (S) protein after the third dose in both groups, although nAbs in KTR were lower than controls. nAbs against pseudoviruses expressing the Omicron S protein were low in both groups, with no increase after the 3rd dose in KTR. Reactivity of CD4+ T cells after boosting was observed when cells were challenged with Wuhan-Hu-1 S peptides, while Omicron S peptides were less effective in both groups. IFN-γ production was detected in KTR in response to ancestral S peptides, confirming antigen-specific T cell activation. Our study demonstrates that the 3rd mRNA dose induces T cell response against Wuhan-Hu-1 spike peptides in KTR, and an increment in the humoral immunity. Instead, humoral and cellular immunity to Omicron variant immunogenic peptides were low in both KTR and healthy vaccinated subjects.

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“…A meta-analysis by Manothummetha et al also indicated that Rmab use within 1 year was associated with a risk of decreased antibody acquisition rate [ 17 ]. Takai et al showed that the antibody acquisition rate is low within 2 years after Rmab administration in kidney transplant patients [ 18 ]; however, the longer-term effects of Rmab have not been investigated. It should be noted that B cells may be suppressed for nearly 5 years with adequate maintenance therapy, as revealed in this study.…”

Section: Discussionmentioning

confidence: 99%

Impact of B Cell Depletion on COVID-19 in Kidney Transplant Recipients

Aida

Ito

Kurihara

et al. 2023

Viruses

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Kidney transplant recipients are patients at high risk for coronavirus disease 2019 (COVID-19) due to being on immunosuppressive therapy. B cell depletion therapy, including rituximab, is an important strategy for ABO-incompatible transplants. However, knowledge about the effect of B cell depletion therapy on COVID-19 is lacking. Thirty kidney transplant recipients who developed COVID-19 were included in this study. To examine the impact of B cell depletion therapy, we retrospectively investigated the relationship between the background of the patients and the clinical outcome. Of the 30 patients, 13 received B cell depletion therapy. The median time between transplant and onset of COVID-19 was 6.1 years after transplantation; however, nine cases remained markedly depleted of CD19(+) cells (<4.0%). The patients were assigned to the normal (n = 21) and depletion groups (n = 9). Progression rates in the depletion and normal groups were 55.6% and 9.5%, respectively (p = 0.014). Furthermore, the survival rate was significantly lower in the depletion group (100% in the normal group vs. 66.7% in the depletion group; p = 0.021). B cell depletion therapy may have long-term effects and increase the risk of COVID-19 in kidney transplant recipients.

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Humoral and cellular immune response and the safety of third SARS-CoV-2 mRNA vaccine with longer interval after the second vaccination in kidney transplant recipients

Cited by 9 publications

References 31 publications

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV

Booster Dose of SARS-CoV-2 mRNA Vaccine in Kidney Transplanted Patients Induces Wuhan-Hu-1 Specific Neutralizing Antibodies and T Cell Activation but Lower Response against Omicron Variant

Impact of B Cell Depletion on COVID-19 in Kidney Transplant Recipients

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