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Booster shot of inactivated SARS-CoV-2 vaccine induces potent immune responses in people living with HIV.

ABSTRACT: This study aimed to investigate the immunogenicity to SARS-CoV-2 and evasive subvariants BA.4/5 in people living with HIV (PLWH) following a third booster shot of inactivated SARS-CoV-2 vaccine. We conducted a cross-sectional study in 318 PLWH and 241 healthy controls (HC) using SARS-CoV-2 immunoassays. Vaccine-induced immunological responses were compared before and after the third dose. Serum levels of IgG anti-RBD and inhibition rate of NAb were significantly elevated at the "post-third dose" sampling time compared with the pre-third dose in PLWH, but were relatively decreased in contrast with those of HCs. Induced humoral and cellular responses attenuated over time after triple-dose vaccination. The neutralizing capacity against BA.4/5 was also intensified but remained below the positive inhibition threshold. Seropositivity of SARS-CoV-2-specific antibodies in PLWH was prominently lower than that in HC. We also identified age, CD4 cell counts, time after the last vaccination, and WHO staging type of PLWH as independent factors associated with the seropositivity of antibodies. PLWH receiving booster shot of inactivated vaccines generate higher antibody responses than the second dose, but lower than that in HCs. Decreased anti-BA.4/5 responses than that of WT impede the protective effect of the third dose on Omicron prevalence.

SUBMITTER: Zhan H

PROVIDER: S-EPMC9880704 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Booster shot of inactivated SARS-CoV-2 vaccine induces potent immune responses in people living with HIV.

Zhan Haoting H Gao Huixia H Liu Yongmei Y Zhang Xihong X Li Haolong H Li Xiaomeng X Wang Lijing L Li Chen C Li Beilei B Wang Yuling Y Dai Erhei E Li Yongzhe Y

Journal of medical virology 20230101 1

This study aimed to investigate the immunogenicity to SARS-CoV-2 and evasive subvariants BA.4/5 in people living with HIV (PLWH) following a third booster shot of inactivated SARS-CoV-2 vaccine. We conducted a cross-sectional study in 318 PLWH and 241 healthy controls (HC) using SARS-CoV-2 immunoassays. Vaccine-induced immunological responses were compared before and after the third dose. Serum levels of IgG anti-RBD and inhibition rate of NAb were significantly elevated at the "post-third dose" ...[more]

PMID: 36571267

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Project description:BackgroundsTo date, the effects of SARS-CoV-2 vaccines on people living with HIV (PLWH) were mainly focused on messenger RNA (mRNA) and adenovirus vector-based vaccines, and little is known about the effects of inactivated virus-based vaccine. This study was designed to determine the effects of inactivated SARS-CoV-2 vaccines on PLWH.MethodsTwenty-four HIV-positive individuals and 24 healthy donors (HD) were respectively recruited from Malipo Country People's Hospital and community in Kunming city. Enumeration of lymphocyte and CD4+CD45RO+ memory T cells were evaluated by flow cytometry. Competitive ELISA was used to measure the level of Anti-SARS-CoV-2 neutralization antibody. Spearman or Pearson correlation analysis was used to analyze the relationship between laboratory indicators and neutralization antibodies in PLWH. T-cell responses (Th1, Th2, Th17, Treg) and intracellular expression of cytokines (IL-2 and TNF-α) in CD4 or CD8 were induced by spike protein in SARS-CoV-2 (SARS-2-S) and further measured by intracellular staining.ResultsCD4, B cells, CD4+CD45RO+ memory T cells in peripheral blood of PLWH are dramatically decreased in comparison with HD. Importantly, PLWH display comparable neutralizing antibody positive rate to HD after inoculation with inactivated SARS-CoV-2 vaccine. However, PLWH showed weaker responses to vaccines exhibited by lower levels of neutralizing antibodies. Correlation analysis shows that this is possibly caused by low number of CD4 and B cells. Furthermore, SARS-2-S-induced Th2 and Th17 responses are also decreased in PLWH, while no influences on Treg and other cytokines (IL-2, TNF-α and IFN-γ) observed.ConclusionsPLWH and HD have comparable neutralizing antibodies positive rates, but PLWH display weaker responses to inactivated SARS-CoV-2 vaccines in magnitude, which suggests that a booster dose or dose adjustment are required for HIV-infected individuals, especially for those with lower counts of CD4 T and B cells.

Project description:BackgroundMulti-types COVID-19 vaccines have shown safety and efficacy against COVID-19 in adults. Although current guidelines encourage people living with HIV (PLWH) to take COVID-19 vaccines, whether their immune response to COVID-19 vaccines is distinct from HIV-free individuals is still unclear.MethodsBetween March to June 2021, 48 PLWH and 40 HNC, aged 18 to 59 years, were enrolled in the study in Wuchang district of Wuhan city. All of them received inactivated COVID-19 vaccine (Sinopharm, WIBP-CorV, Wuhan Institute of Biological Products Co. Ltd) at day 0 and the second dose at day 28. The primary safety outcome was the combined adverse reactions within 7 days after each injection. The primary immunogenicity outcomes were SARS-CoV-2 neutralizing antibodies (nAbs) responses by chemiluminescence and total specific IgM and IgG antibodies responses by ELISA and colloidal gold at baseline (day 0), day 14, day 28, day 42, and day 70.ResultsIn total, the study included 46 PLWH and 38 HNC who finished 70 days' follow-up. The frequency of adverse reactions to the first and second dose was not different between PLWH (30% and 11%) vs. HNC (32% and 24%). NAbs responses among PLWH peaked at day 70, while among HNC peaked at day 42. At day 42, the geometric mean concentration (GMC) and seroconversion rate of nAbs among PLWH were 4.46 binding antibody units (BAU)/mL (95% CI 3.18-5.87) and 26% (95% CI 14-41), which were lower than that among HNC [GMC (18.28 BAU/mL, 95% CI 10.33-32.33), seroconversion rate (63%, 95% CI 44-79)]. IgG responses among both PLWH and HNC peaked at day 70. At day 70, the geometric mean ELISA units (GMEU) and seroconversion rate of IgG among PLWH were 0.193 ELISA units (EU)/mL (95% CI 0.119-0.313) and 51% (95% CI 34-69), which was lower than that among HNC [GMEU (0.379 EU/mL, 95% CI 0.224-0.653), seroconversion rate (86%, 95% CI 64-97)]. There were no serious adverse events.ConclusionsEarly humoral immune response to the inactivated COVID-19 vaccine was weaker and delayed among the PLWH population than that among HNC. This observation remained consistent regardless of a high CD4 count with effective antiretroviral therapy.

Project description:Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.

Project description:BackgroundInactivated COVID-19 vaccines are safe and effective in the general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH).Methods42 HIV-1 infected individuals who were stable on combination antiretroviral therapy (cART) and 28 healthy individuals were enrolled in this open-label two-arm non-randomized study at Hubei Provincial Center for Disease Control and Prevention, China. Two doses of an inactivated COVID-19 vaccine (BBIBP-CorV) were given on April 22, 2021 and May 25, 2021, respectively. The reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry.FindingsAll the HIV-1 infected participants had a CD4+ T cell count >200 cells/μL both at baseline (659·0 ± 221·9 cells/μL) and 4 weeks after vaccination (476·9 ± 150·8 cells/μL). No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. PLWH with low baseline CD4+/CD8+ T cell ratios (<0·6) generated lower antibody responses after vaccination than PLWH with medium (0·6∼1·0) or high (≥1·0) baseline CD4+/CD8+ T cell ratios (P<0·01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination (P<0·0001), but it did not lead to any adverse clinical manifestation. Moreover, we found that the general HIV-1 viral load among the PLWH cohort decreased significantly after vaccination (P=0·0192). The alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation (P>0·2).InterpretationOur data demonstrated that the inactivated SARS-CoV-2 vaccine was safe, immunogenic in PLWH who are stable on cART with suppressed viral load and CD4+ T cell count > 200 cells/μL. However, the persistence of the vaccine-induced immunities in PLWH need to be further investigated.

Project description:ObjectiveBoth B-cell- and T-cell-mediated immunity are crucial for the effective clearance of viral infection, but little is known about the dynamic characteristics of SARS-CoV-2-specific B-cell and T-cell responses in people living with HIV (PLWH) after a full course of inactivated SARS-CoV-2 vaccination.MethodsIn this study, fifty people living with HIV (PLWH) and thirty healthy controls (HCs) were enrolled to assess B-cell and T-cell responses at the day before the vaccination (T0), two weeks after the first dose (T1), two months after the first dose (T2), the day of the third dose (T3), one month after the third dose (T4), three months after the third dose (T5) and 12 months (T6) after the third dose.ResultsSARS-CoV-2-specific B-cell and T-cell responses were induced in people living with HIV (PLWH), and these responses lasted at least one year after the third vaccine dose. However, the peak frequencies of Spike-specific B-cell and T-cell responses in PLWH were lower than those in HIV-negative controls. In addition, the expansion of activated B cells, memory B cells and plasma cells after primary vaccination was observed, but the percentages of these cells were decreased at T6 and were comparable to those at T0. Additionally, the percentages of activated T cells, exhausted T cells and SARS-CoV-2-specific T cells with enhanced functional activity were increased following the administration of inactivated SARS-CoV-2 vaccine. In addition, PLWH had lower percentages of plasma cells, RBD-specific B cells, circulating Tfh (cTfh) cells and CD38+ cTfh cells, and the percentages of the latter two types of cells were positively correlated with the titer of neutralizing antibodies, indicating these differences may account for the weaker immune responses induced in PLWH.ConclusionThese data suggest that specific B-cell and T-cell responses could be sustained for at least one year after receiving the third vaccination. Our findings emphasize that the weak SARS-CoV-2-specific B-cell and T-cell responses induced in PLWH have implications for clinical decision-making and public health policy for PLWH with respect to SARS-CoV-2 infection.

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Booster shot of inactivated SARS-CoV-2 vaccine induces potent immune responses in people living with HIV.

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Booster shot of inactivated SARS-CoV-2 vaccine induces potent immune responses in people living with HIV.

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