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Comparable antigen-specific T cell responses in vaccinees with diverse humoral immune responses after the primary and booster BBIBP-CorV vaccination.

ABSTRACT: BBIBP-CorV exerts efficient protection against SARS-CoV-2 infection. However, waning vaccine-induced humoral immune responses after two-dose vaccination have significantly undermined durable immuno-protection. In this study, we have demonstrated that although anti-spike (S) antibody responses in BBIBP-CorV vaccinees exhibited three serotypes after 6 months, including de novo sero-negative, sero-positive, and sero-decay features, S-specific interferon-γ release as well as Th1 cytokine production in CD4⁺ and CD8⁺ T cells were comparable, especially in vaccinees without detectable neutralizing antibodies. Notably, regardless of dramatic increases in humoral immunity after booster vaccination, T cell responses targeting S protein from either wild type or Omicron remained stable before and after booster vaccination in all three serotype vaccinees. No severe cases were observed even in the sero-decay group during the Omicron epidemic in Shanghai. Our results thus illustrate that unlike fluctuating humoral responses, viral-specific T cell responses are extremely stable after booster vaccination. Sustained T cell responses might be dedicated to the rapid restoration of antibody responses after booster vaccination.

SUBMITTER: Wei D

PROVIDER: S-EPMC9621266 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Comparable antigen-specific T cell responses in vaccinees with diverse humoral immune responses after the primary and booster BBIBP-CorV vaccination.

Wei Dong D Chen Yingying Y Yu Xiaoqi X Lai Yang-Dian YD Xu Wenxin W Ji Ping P Yang Zhitao Z Chen Erzhen E Zhang Xinxin X Wang Ying Y

Emerging microbes & infections 20221201 1

BBIBP-CorV exerts efficient protection against SARS-CoV-2 infection. However, waning vaccine-induced humoral immune responses after two-dose vaccination have significantly undermined durable immuno-protection. In this study, we have demonstrated that although anti-spike (S) antibody responses in BBIBP-CorV vaccinees exhibited three serotypes after 6 months, including <i>de novo</i> sero-negative, sero-positive, and sero-decay features, S-specific interferon-γ release as well as Th1 cytokine prod ...[more]

PMID: 36166417

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Project description:The kinetics and magnitude of antibody responses to different proteins of the SARS-CoV-2 virus in Sinopharm/BBIBP-CorV vaccinees has not been previously studied. Therefore, we investigated antibody responses to different SARS-CoV-2 proteins at 2 weeks, 3 months, and 6 months post-second dose in previously infected (n = 20) and uninfected (n = 20) Sinopharm/BBIBP-CorV vaccinees. The IgG antibodies to the S, S1 and S2 and N were several folds higher in those who had natural infection compared to uninfected individuals at all time points. We then compared the persistence of antibody responses and effect of natural omicron infection or BNT162b2 booster in Sinopharm/BBIBP-CorV vaccinees. We measured the total antibodies to the RBD, ACE2 blocking antibodies and antibody responses to different SARS-CoV-2 proteins in Sinopharm vaccinees at 7 months post second dose, including those who remained uninfected and not boosted (n = 21), or those who had previous infection and who did not obtain the booster (n = 17), those who were not infected, but who received a BNT162b2 booster (n = 30), or those who did not receive the booster but were infected with omicron (n = 29). At 7 months post second dose uninfected (no booster) had the lowest antibody levels to the RBD, while omicron infected vaccinees showed significantly higher anti-RBD antibody levels (p = 0.04) than vaccinees who received the booster. Only 3/21 cohort A (14.3%) had ACE2 blocking antibodies, while higher frequencies were observed in naturally infected individuals (100%), those who received the booster (18/21, 85.7%), and omicron infected individuals (100%). Pre-vaccination, naturally infected had the highest antibody levels to the N protein. These data suggest that those previously infected Sinopharm/BBIBP-CorV vaccinees have a robust antibody response, 7 months post vaccination, while vaccinees who were naturally infected with omicron had a similar immune response to those who received the booster. It will be important to investigate implications for subsequent clinical protection.

Project description:The effectiveness of COVID-19 vaccines developed against the original virus strain deteriorated noticeably in efficacy against the Omicron variant (B.1.1.529). Moreover, the immunity developed after vaccination or due to natural infection rapidly waned. In the present study, covering this period, we summarize the incidence of breakthrough infections among healthcare workers (HCWs) with respect to administration of the three vaccine doses. Additionally, we evaluate the long-term SARS-CoV-2-specific humoral and T cell responses at two different time points: six and twelve months after receipt of the third (booster) dose. The spike-protein-specific antibody levels and the quantity of structural-protein-specific T cells were evaluated at these time points and compared with the values measured earlier, 14 days after the booster vaccination. The study participants were categorized into two cohorts: Members of the first cohort received a two-dose BNT162b2 mRNA-based vaccine regimen, followed by an additional BNT162b2 booster six months later. Individuals in the second cohort received an inactivated-virus-based BBIBP-CorV booster six months after the initial two-dose BNT162b2 vaccination. Overall, 64.3% of participants were infected with SARS-CoV-2 confirmed by PCR or antigen test; however, additional subjects from the first cohort (23%) who did not know about their previous infection but had an anti-nucleocapsid T cell response were also considered virus-experienced. According to our results, no statistically significant difference was found between the two cohorts regarding the SARS-CoV-2-specific T cell response, neutralizing anti-RBD IgG, and anti-S IgA serum antibody levels either six or twelve months after receiving the booster, despite the overall higher median values of the first cohort. The only significant difference was the higher anti-S1/S2 IgG antibody level in the first cohort one year after the BNT162b2 booster (p = 0.039). In summary, the BNT162b2 and BBIBP-CorV boosters maintain durable humoral and T cell-mediated immune memory even one year after application. Although the booster provided limited protection against Omicron breakthrough infections, as 73.6% of these infections occurred after the booster vaccination, which means 53.5% cumulative incidence, it still offered excellent protection against severe disease and hospitalization in both cohorts.

Project description:BackgroundVaccination has proven the potential to control the COVID-19 pandemic worldwide. Although recent evidence suggests a poor humoral response against SARS-CoV-2 in vaccinated hematological disease (HD) patients, data on vaccination in these patients is limited with the comparison of mRNA-based, vector-based or inactivated virus-based vaccines.MethodsForty-nine HD patients and 46 healthy controls (HCs) were enrolled who received two-doses complete vaccination with BNT162b2, or AZD1222, or BBIBP-CorV, respectively. The antibodies reactive to the receptor binding domain of spike protein of SARS-CoV-2 were assayed by Siemens ADVIA Centaur assay. The reactive cellular immunity was assayed by flow cytometry. The PBMCs were reactivated with SARS-CoV-2 antigens and the production of activation-induced markers (TNF-α, IFN-γ, CD40L) was measured in CD4+ or CD8+ T-cells ex vivo.ResultsThe anti-RBD IgG level was the highest upon BNT162b2 vaccination in HDs (1264 BAU/mL) vs. HCs (1325 BAU/mL) among the studied groups. The BBIBP-CorV vaccination in HDs (339.8 BAU/mL ***p < 0.001) and AZD1222 in HDs (669.9 BAU/mL *p < 0.05) resulted in weaker antibody response vs. BNT162b2 in HCs. The response rate of IgG production of HC vs. HD patients above the diagnostic cut-off value was 100% vs. 72% for the mRNA-based BNT162b2 vaccine; 93% vs. 56% for the vector-based AZD1222, or 69% vs. 33% for the inactivated vaccine BBIBP-CorV, respectively. Cases that underwent the anti-CD20 therapy resulted in significantly weaker (**p < 0.01) anti-RBD IgG level (302 BAU/mL) than without CD20 blocking in the HD group (928 BAU/mL). The response rates of CD4+ TNF-α+, CD4+ IFN-γ+, or CD4+ CD40L+ cases were lower in HDs vs. HCs in all vaccine groups. However, the BBIBP-CorV vaccine resulted the highest CD4+ TNF-α and CD4+ IFN-γ+ T-cell mediated immunity in the HD group.ConclusionWe have demonstrated a significant weaker overall response to vaccines in the immunologically impaired HD population vs. HCs regardless of vaccine type. Although, the humoral immune activity against SARS-CoV-2 can be highly evoked by mRNA-based BNT162b2 vaccination compared to vector-based AZD1222 vaccine, or inactivated virus vaccine BBIBP-CorV, whereas the CD4+ T-cell mediated cellular activity was highest in HDs vaccinated with BBIBP-CorV.

Project description:Several observational studies have confirmed that the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) might substantially affect the gastrointestinal (GI) system by replicating in human small intestine enterocytes. Yet, so far, no study has reported the effects of inactivated SARS-CoV-2 virus vaccines on gut microbiota alterations. In this study, we examined the effects of the BBIBP-CorV vaccine (ChiCTR2000032459, sponsored by the Beijing Institute of Biological Products/Sinopharm), on gut microbiota. Fecal samples were collected from individuals whoreceived two doses of intramuscular injection of BBIBP-CorV and matched unvaccinated controls. DNA extracted from fecal samples was subjected to 16S ribosomal RNA sequencing analysis. The composition and biological functions of the microbiota between vaccinated and unvaccinated individuals were compared. Compared with unvaccinated controls, vaccinated subjects exhibited significantly reduced bacterial diversity, elevated firmicutes/bacteroidetes (F/B) ratios, a tendency towards Faecalibacterium-predominant enterotypes, and altered gut microbial compositions and functional potentials. Specifically, the intestinal microbiota in vaccine recipients was enriched with Faecalibacterium and Mollicutes and with a lower abundance of Prevotella, Enterococcus, Leuconostocaceae, and Weissella. Microbial function prediction by phylogenetic investigation of communities using reconstruction of unobserved states (PICRUSt) analysis further indicated that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in carbohydrate metabolism and transcription were positively associated with vaccine inoculation, whereas capacities in neurodegenerative diseases, cardiovascular diseases, and cancers were negatively affected by vaccines. Vaccine inoculation was particularly associated with gut microbiota alterations, as was demonstrated by the improved composition and functional capacities of gut microbiota.

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Comparable antigen-specific T cell responses in vaccinees with diverse humoral immune responses after the primary and booster BBIBP-CorV vaccination.

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Comparable antigen-specific T cell responses in vaccinees with diverse humoral immune responses after the primary and booster BBIBP-CorV vaccination.

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