Project description:Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.
Project description:To compare the effects of different types of SARS-CoV-2 vaccines in booster immunization, this study established a population cohort vaccinated with inactivated vaccine and protein subunit vaccine as the third booster vaccine, respectively. We collected serum and PBMC samples from participants in chronological order, and performed a systematic review of distinct antibody signatures and microtranscriptomics to provide data support for booster immunization.
Project description:COVID-19 vaccination is the most effective approach to prevent severe disease and death. Inactivated vaccines are the most accessible type of COVID-19 vaccines in the developing countries. Several studies, including work from our group, have demonstrated that the third (booster) dose of inactivated COVID-19 vaccine induces robust humoral and cellular immune responses. The aim of this study was to examine miRNA expression profile in participants received a homogenous third dose of the CoronaVac vaccine.
Project description:We have reported that IgG antibody responses following two mRNA COVID-19 vaccinations are impaired among patients with multiple myeloma (MM). In the current study, sixty-seven patients with MM were tested for anti-spike IgG antibodies 0-60 days prior to their first vaccination, 14-28 days following the second dose, and both before and 14-28 days after their third dose of the mRNA-1273 or BNT162b2 vaccines. After the first two doses, most patients' (93 %) antibody levels declined to ineffective levels (<250 BAU/mL) prior to their third dose (D3). D3 elicited responses in 84 % of patients (61 % full response and 22 % partial response). The third vaccination increased antibody levels (average = 370.4 BAU/mL; range, 1.0-8977.3 BAU/mL) relative to just prior to D3 (average = 25.0 BAU/mL; range, 1.0-683.8 BAU/mL) and achieved higher levels than peak levels after the first two doses (average = 144.8 BAU/mL; range, 1.0-4,284.1 BAU/mL). D3 response positively correlated with mRNA-1273, a > 10-fold change from baseline for the two-dose series, switching from BNT162b2 to mRNA-1273 for D3, and treatment with elotuzumab and an immunomodulatory agent. Lower antibody levels prior to D3, poorer overall response to first two doses, and ruxolitinib or anti-CD38 monoclonal antibody treatment negatively correlated with D3 response. Our results show encouraging activity of the third vaccine, even among patients who failed to respond to the first two vaccinations. The finding of specific factors that predict COVID-19 antibody levels will help advise patients and healthcare professionals on the likelihood of responses to further vaccinations.
Project description:Background and aimsCirrhosis is associated with immune dysregulation and hypo-responsiveness to several vaccines including against COVID-19. Our aim was to study the association of the receipt of three doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines in patients with cirrhosis, compared to a propensity-matched control group of patients at similar risk of infection who received two doses.MethodsThis was a retrospective cohort study of patients with cirrhosis who received two or three doses of a COVID-19 mRNA vaccine at the Veterans Health Administration. Participants who received three doses of the vaccine (n=13,041) were propensity matched with 13,041 controls who received two doses, and studied between July 18, 2021 and February 11, 2022, when B.1.617.2 (Delta) and B.1.1.529 (Omicron) were the predominant variants. Outcomes were aggregated as all cases with COVID-19, symptomatic COVD-19, with at least moderate COVID-19, or severe or critical COVID-19.ResultsReceipt of the third dose of a COVID-19 mRNA vaccine was associated with an 80.7% reduction COVID-19 (95% CI 39.2-89.1, p<0.001), 80.4% reduction in symptomatic COVID-19, 80% reduction in moderate/ severe or critical COVID-19, (95% CI 34.5-87.6%, p=0.005), 100% reduction in severe or critical COVID-19 (95% CI 99.2-100.0, p=0.01), and a 100% reduction in COVID-19-related death (95% CI 99.8-100.0, p=0.007). The magnitude of reduction in COVID-19 was greater with the third dose of BNT 162b2 than mRNA-1273 and among participants with compensated than decompensated cirrhosis.ConclusionsAdministration of a third dose of a COVID-19 mRNA vaccine was associated with a more significant reduction in COVID-19 in cirrhosis than reported in the general population, suggesting that the third dose can overcome vaccine hyporesponsiveness in this population.Lay summaryCirrhosis is associated with decreased responsiveness to several vaccines, including against COVID-19. In this study of 26,082 participants with cirrhosis during the delta and omicron surge, receipt of the third dose of the vaccine was associated with 80% reduction in COVID-19, 100% reduction in severe/critical COVID-19, and 100% reduction in COVID-19-related death. The findings support the third dose of mRNA vaccine among patients with cirrhosis.
Project description:ObjectivesThe SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs).MethodsWe analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant in 113 SOTRs, of whom 44 had recovered from COVID-19 (recovered-SOTRs) and 69 had not contracted the virus (COVID-naïve). In addition, 30 HCs, 8 of whom had recovered from COVID-19, were also studied.ResultsHere, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti-viral antibodies against all viral strains in the fully vaccinated COVID-naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti-RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered-SOTRs who received two doses of vaccine demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron.ConclusionThese findings illustrate a significant impact of previous infection on the development of anti-SARS-CoV-2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.