mRNA-1273 Vaccine Research Articles

Determinants of protective humoral response to mRNA-1273 and BNT162b2 vaccines in peritoneal dialysis patients: a prospective cohort study

Patients with chronic kidney disease (CKD) on dialysis have a higher mortality rate associated with SARS-CoV-2 infection. Although vaccines are now available, the protective response rates and determinants of humoral response to the vaccine are poorly described in patients on peritoneal dialysis. This was a prospective observational study describing the response rates of detectable and standardized protective antibody titers one month after each mRNA vaccine dose in a cohort of 88 patients on peritoneal dialysis. We found that the vast majority of patients produced protective levels of antibodies (73%) one month after the second vaccine dose. In the multivariate analysis, the single determinant for an adequate humoral response was the weekly Kt/V, a surrogate of dialysis dose. The response rate was higher, but not significantly, with the mRNA-1273 than with the BNT162b2 vaccine one month after the second dose (78.7 vs. 46.2%, respectively, p = 0.02). We found that patients on peritoneal dialysis had a satisfactory humoral response rate, which was much higher than in transplant recipients. PD patients with a poor humoral response, particularly those with a low wKT/V, may benefit from an additional dose of vaccine.

Robust immune response to COVID-19 vaccination in the island population of Greenland

BackgroundIn Greenland, the COVID-19 pandemic was characterised by a late onset of community transmission and a low impact on the healthcare system, hypothesised as being partly due to a high uptake of vaccinations. To underpin this description, we aimed to assess the SARS-CoV-2 immune response post-vaccination in a Greenlandic population.MethodsIn this observational cohort study, we included 430 adults in Greenland who had received a complete two-dose SARS-CoV-2 vaccination at enrolment. The total plasma SARS-CoV-2 spike glycoprotein Ig antibodies (S-Ab) induced by either the BNT162b2 or mRNA-1273 vaccine, was measured up to 11 months after the second vaccine dose. In addition, total salivary S-Abs were examined in 107 participants, and the T-cell response to the spike glycoprotein was assessed in 78 participants out of the entire study cohort.ResultsHere we demonstrate that two months after the second vaccine dose, 96% of participants have protective plasma S-Ab levels. By 11 months, 98% have protective levels, with prior SARS-CoV-2 infection particularly enhancing S-Ab levels by 37% (95% CI 25–51%). Among individuals aged 60 years and older, we observe a 21% (95% CI 7–33%) reduction in antibody response. Total salivary S-Ab levels are detectable in all participants and significantly correlate with plasma levels. Moreover, all participants exhibit a robust SARS-CoV-2-specific T-cell response 11 months post-primary vaccination.ConclusionsOur findings show that Greenlanders exhibit a robust and lasting immune response, both humoral and cellular, comparable to other population groups up to at least 11 months after the second vaccine dose. These results corroborate the hypothesis that vaccines contributed to the mild impact of the COVID-19 pandemic in the Greenlandic population.

The descriptive epidemiology of adverse events following two doses of mRNA COVID-19 vaccination in Curaçao, the Caribbean

Background BNT162b2 and mRNA-1273 COVID-19 vaccines have been used for mass vaccinations in Curaçao, the Caribbean but information on adverse events (AEs)in this population is unavailable. This study describes the characteristics of vaccinees that incurred AEs, explores the associations between AEs by vaccine and doses, and estimates the rate of AEs. Methods Vaccination and AEs data for all persons of age 5 years (range 5–105 years) and older who received two doses of COVID-19 vaccine at 71 centres in Curaçao between February 24, 2021, and April 5, 2023, were included in this retrospective observational study. Results The vaccines differed significantly in the frequency distribution of vaccinees by age, age groups, sex, AEs, and prior COVID-19 infection. Occurrence of AEs was strongly associated with mRNA vaccine brand, sex, number of doses, but not with age, age group, and prior COVID-19 infection. Of 209,720 doses, 84 persons (0.04%) incurred AEs following two doses of mRNA vaccines (overall rate of 40.1 per 100,000 persons (95% CI 32.4–49.6). AEs were also significantly higher in females compared to males.AE rates associated with BNT162b2, and mRNA-1273 vaccines were low, but BNT162b2 vaccinees incurred substantially significantly higher AE rates (58.3 per 100,000 persons, 95% CI 45.4–74.9) than mRNA-1273 vaccinees (21.9 per 100,000 persons, 95% CI 14.6–32.8). mRNA-1273 vaccine was associated with a significantly lower risk of AEs. Conclusions AE reporting varied by age, sex, and vaccine used as well as the number of doses. Future studies with follow-up and longer-term reporting of AEs should be conducted.

Salivary immune responses after COVID-19 vaccination.

mRNA-based COVID-19 vaccines have played a critical role in reducing severe outcomes of COVID-19. Humoral immune responses against SARS-CoV-2 after vaccination have been extensively studied in blood; however, limited information is available on the presence and duration of SARS-CoV-2 specific antibodies in saliva and other mucosal fluids. Saliva offers a non-invasive sampling method that may also provide a better understanding of mucosal immunity at sites where the virus enters the body. Our objective was to evaluate the salivary immune response after vaccination with the COVID-19 Moderna mRNA-1273 vaccine. Two hundred three staff members of the U.S. Centers for Disease Control and Prevention were enrolled prior to receiving their first dose of the mRNA-1273 vaccine. Participants were asked to self-collect 6 saliva specimens at days 0 (prior to first dose), 14, 28 (prior to second dose), 42, and 56 using a SalivaBio saliva collection device. Saliva specimens were tested for anti-spike protein SARS-CoV-2 specific IgA and IgG enzyme immunoassays. Overall, SARS-CoV-2-specific salivary IgA titers peaked 2 weeks after each vaccine dose, followed by a sharp decrease during the following weeks. In contrast to IgA titers, IgG antibody titers increased substantially 2 weeks after the first vaccine dose, peaked 2 weeks after the second dose and persisted at an elevated level until at least 8 weeks after the first vaccine dose. Additionally, no significant differences in IgA/IgG titers were observed based on age, sex, or race/ethnicity. All participants mounted salivary IgA and IgG immune responses against SARS-CoV-2 after receiving the mRNA-1273 COVID-19 vaccine. Because of the limited follow-up time for this study, more data are needed to assess the antibody levels beyond 2 months after the first dose. Our results confirm the potential utility of saliva in assessing immune responses elicited by immunization and possibly by infection.

Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases

Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites. The open-label (Parts B and C) primary objectives were evaluation of long-term safety and effectiveness of primary vaccination plus a 50-µg booster dose; immunogenicity was a secondary objective. Of 29,035 open-label participants, 19,609 received boosters (mRNA-1273 [n = 9647]; placebo-mRNA-1273 [n = 9952]; placebo [n = 10] groups). Booster safety was consistent with that reported for primary vaccination. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with a significant, 47.0% (95% CI : 39.0-53.9%) reduction of Omicron BA.1 incidence (24.6 [23.4 − 25.8] vs 46.4 [40.6 − 52.7]/1000 person-months). In an exploratory Cox regression model adjusted for time-varying covariates, a longer median interval between primary vaccination and boosting (mRNA-1273 [13 months] vs placebo-mRNA-1273 [8 months]) was associated with significantly lower, COVID-19 risk (24.0% [16.0% − 32.0%]) during Omicron BA.1 predominance. Boosting elicited greater immune responses against SARS-CoV-2 than primary vaccination, irrespective of prior SARS-CoV-2 infection. Primary vaccination and boosting with mRNA-1273 demonstrated acceptable safety, effectiveness and immunogenicity against COVID-19, including emergent variants.

MRNA-1273 vaccination induces polyfunctional memory CD4 and CD8 T cell responses in patients with solid cancers undergoing immunotherapy or/and chemotherapy.

Research has confirmed the safety and comparable seroconversion rates following SARS-CoV-2 vaccination in patients with solid cancers. However, the impact of cancer treatment on vaccine-induced T cell responses remains poorly understood. In this study, we expand on previous findings within the VOICE trial by evaluating the functional and phenotypic composition of mRNA-1273-induced T cell responses in patients with solid tumors undergoing immunotherapy, chemotherapy, or both, compared to individuals without cancer. We conducted an ELISpot analysis on 386 participants to assess spike-specific T cell responses 28 days after full vaccination. Further in-depth characterization of using flow cytometry was performed on a subset of 63 participants to analyze the functional phenotype and differentiation state of spike-specific T cell responses. ELISpot analysis showed robust induction of spike-specific T cell responses across all treatment groups, with response rates ranging from 75% to 80%. Flow cytometry analysis revealed a distinctive cytokine production pattern across cohorts, with CD4 T cells producing IFNγ, TNF, and IL-2, and CD8 T cells producing IFNγ, TNF, and CCL4. Variations were observed in the proportion of monofunctional CD4 T cells producing TNF, particularly higher in individuals without cancer and patients treated with chemotherapy alone, while those treated with immunotherapy or chemoimmunotherapy predominantly produced IFNγ. Despite these differences, polyfunctional spike-specific memory CD4 and CD8 T cell responses were comparable across cohorts. Notably, immunotherapy-treated patients exhibited an expansion of spike-specific CD4 T cells with a terminally differentiated effector memory phenotype. These findings demonstrate that systemic treatment in patients with solid tumors does not compromise the quality of polyfunctional mRNA-1273-induced T cell responses. This underscores the importance of COVID-19 vaccination in patients with solid cancers undergoing systemic treatment.

Patterns and predictors of COVID-19 vaccination among young adults at 44 US sites: Secondary analysis of a randomized, controlled, open-label trial, March – December 2021

Background: The introduction of vaccines during the COVID-19 pandemic provided an opportunity to slow transmission of SARS-CoV-2, but initial uptake of COVID-19 vaccination was slow. We analyzed data from a randomized clinical trial of the mRNA-1273 vaccine (NCT04811664) to describe the patterns of uptake of COVID-19 vaccines among young adults.Methods: The CoVPN 3006 trial randomized adults ages 18–29 from 44 sites in the United States to receive 1) immediate mRNA-1273 vaccination from the study site, or 2) standard of care, including the option to seek vaccination at any time in the future. Randomization occurred between March and November 2021, and an observational arm of adults who declined vaccination was enrolled beginning June 2021. Among participants in the standard of care (SoC) or Vaccine Declined arms, we estimated demographic, behavioral, and health history correlates of vaccination, and the four-month cumulative incidence of COVID-19 vaccination using inverse probability weighted Kaplan-Meier estimators.Results: Among 728 SoC and 470 Vaccine Declined participants, 79% and 16% received COVID-19 vaccination, respectively. SoC and Vaccine Declined participants were more likely to seek and receive vaccination if they reported COVID-19 preventive behaviors, including wearing masks, physically distancing, and avoiding large gatherings. We identified strong predictors of vaccination in the Vaccine Declined arm, including attending class in person (adjusted risk ratio [aRR]: 0.47, 95% confidence interval [CI] 0.21, 1.03), having a COVID-19 relevant medical condition (aRR: 1.95, 95% CI: 0.89, 4.26), and avoiding large gatherings (aRR: 2.24, 95% CI: 1.18, 4.25), though low vaccination rates in this arm led to imprecise estimates.Conclusions: Individuals who initially decline vaccination can be convinced to vaccinate, particularly if they are already practicing other forms of COVID-19 prevention. Continued outreach and education from the scientific community can combat low vaccine confidence.

Multiple vaccine comparison in the same adults reveals vaccine-specific and age-related humoral response patterns: an open phase IV trial

Vaccine responsiveness is often reduced in older adults. Yet, our lack of understanding of low vaccine responsiveness hampers the development of effective vaccination strategies to reduce the impact of infectious diseases in the ageing population. Young-adult (25–49 y), middle-aged (50-64 y) and older-adult ( ≥ 65 y) participants of the VITAL clinical trials (n = 315, age-range: 28-98 y), were vaccinated with an annual (2019–2020) quadrivalent influenza (QIV) booster vaccine, followed by a primary 13-valent pneumococcal-conjugate (PCV13) vaccine (summer/autumn 2020) and a primary series of two SARS-CoV-2 mRNA-1273 vaccines (spring 2021). This unique setup allowed investigation of humoral responsiveness towards multiple vaccines within the same individuals over the adult age-range. Booster QIV vaccination induced comparable H3N2 hemagglutination inhibition (HI) titers in all age groups, whereas primary PCV13 and mRNA-1273 vaccination induced lower antibody concentrations in older as compared to younger adults (primary endpoint). The persistence of humoral responses, towards the 6 months timepoint, was shorter in older adults for all vaccines (secondary endpoint). Interestingly, highly variable vaccine responder profiles overarching multiple vaccines were observed. Yet, approximately 10% of participants, mainly comprising of older male adults, were classified as low responders to multiple vaccines. This study aids the identification of risk groups for low vaccine responsiveness and hence supports targeted vaccination strategies. Trial number: NL69701.041.19, EudraCT: 2019-000836-24.

Vaccine‐induced humoral response of BNT162b2 and mRNA-1273 against BA.1, BA.5, and XBB.1.5. (sub)variants 6 months after a homologous booster: is immunogenicity equivalent?

IntroductionSome studies suggest that the monovalent mRNA-1273 vaccine is more effective than BNT162b2 in producing higher levels of antibodies. However, limited data are available, and the methods used are not directly comparable. Material and methodsBlood samples were obtained before the booster (third dose) and after 14, 90, and 180 days in two similar cohorts who received the original BNT162b2 or mRNA-1273 vaccine designed to target wild type SARS-CoV-2. The aim of our study is to compare their effectiveness by assessing the levels of binding and neutralizing antibodies specifically against each of the BA.1 variant, BA.5 variant, and the XBB.1.5 subvariant. ResultsOnce the peak was reached after two weeks, a drastic decline in binding and neutralizing antibodies was observed up to 6 months after the homologous booster administration. The humoral response was however more sustained with the mRNA-1273 booster, with half-lives of 167, 55, and 48 days for binding, BA.1, and BA.5 neutralizing antibodies compared to 144, 30, and 29 days for the BNT162b2 booster, respectively. Compared to the BA.1 variant, the neutralizing capacity was significantly decreased at 6 months with the BA.5 variant (fold-decrease: 1.67 to 3.20) and the XBB.1.5. subvariant (fold-decrease: 2.86 to 5.48). ConclusionAlthough the decrease in the humoral response was observed with both mRNA vaccines over time, a more sustained response was observed with the mRNA-1273 vaccine. Moreover, the emergence of Omicron-based variants causes a reduced neutralizing capacity, notably with the XBB.1.5. subvariant. The administration of subsequent boosters would therefore be needed to restore a sufficiently high neutralizing response.

Anti-SARS-CoV-2 antibody dynamics after primary vaccination with two-dose inactivated whole-virus vaccine, heterologous mRNA-1273 vaccine booster, and Omicron breakthrough infection in Indonesian health care workers

BackgroundData on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter.MethodsWe evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI.ResultsOf 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28–90, and IgG titers plateaued between day 90–360. During the BA.1/BA.2 wave (February–March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI.ConclusionsmRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.

Impact of SARS-CoV-2 vaccination in patients with vascular liver diseases: Observations from a VALDIG multicenter study

Background and AimsPatients with vascular liver diseases(VLD) are at higher risk for both severe courses of COVID-19 disease and thromboembolic events. The impact of the SARS-CoV-2 vaccination in VLD patients has not been described and represent the aim of our study. MethodsInternational multicenter prospective observational study in patients with VLD analyzing the incidence of COVID-19 infection after vaccination, severity of side effects, occurrence of thromboembolic events and hepatic decompensation. In a subgroup of patients, the humoral and cellular responses to vaccination were also analyzed. Results898 patients from 14 European centers part of the VALDIG network were included, 872(97.1%) patients received two vaccine doses (fully vaccinated), and 674(75.1%) three doses.Of the total cohort, 151/898 had a COVID-19 infection prior to vaccination, of which 9/151(5.9%) were re-infected. Of the previously 747/898 patients who were not previously infected, 11.2%(84/747) were diagnosed with a COVID-19 infection during the study period.Two infected patients required ICU admission and infection was fatal in two fully vaccinated patients. Main adverse effects were reported in around 40% of patients, being local side effects the most frequent.During the study period, 31(3.5%) patients had thromboembolic events and 21(2.3%) hepatic decompensations. No vaccine-induced-thrombocytopenia (VITT) case was reported.Vaccine immunogenicity was assessed in 36 patients; seroconversion reached 100% and IFNy-T cell responses significant increased post two mRNA-1273 vaccine doses. ConclusionPatients with VLD seems to have a preserved immune response to SARS-CoV-2 vaccination, which appears to be safe and effective in preventing severe COVID-19 infection. Our study cannot definitively establish a direct link between vaccination and thrombotic events, however the contribution of vaccination as a cofactor in VLD remains to be elucidated.

Dog Bite to the Hand: Infectious Disease Considerations

Myocarditis was recently described as one of the complications secondary to COVID-19 vaccination. We present a 38-year-old lady diagnosed with vaccine-related myocarditis a few days after receiving the mRNA-1273 vaccine. We also summarize what is reported in the literature about the association between COVID-19 vaccination and myocarditis. In conclusion, COVID-19 immunization appears to be associated with significantly fewer adverse outcomes than COVID-19 infection among all age groups.

Incidence of adverse events of the Covid-19 vaccine in a population of kidney transplant recipients

Introducción: Early published series suggest that most renal transplant recipients remain at high risk of SARS-CoV-2 infection due to poor humoral response after vaccination. The aim was to study the occurrence of adverse events after two doses of mRNA-1273 vaccine in a population of renal transplant recipients.Material and Method: Analytical, observational, and prospective study. Subjects were injected with two doses of mRNA-1273 vaccine against SARS-CoV-2 according to the schedule established by the laboratory. After injection of each dose, and up to 72 hours later, participants recorded local and/or systemic symptoms and their intensity.Results: 187 patients were included. Eighteen percent of them became infected with SARS-CoV-2 in the pre-vaccination period or between the 1st and 2nd dose. The incidence of adverse events was 91.2%. Of these, the incidence of local (62%) was higher than that of systemic (55%). Past infection was a risk factor for the occurrence of local adverse events after vaccination (OR= 2.4; p=0.045). The same association was detected for systemic adverse events, which were more frequent among those who had passed the disease (OR=3.83; p=0.003).Conclusions: The mRNA-1273 vaccine does not appear to cause serious side effects. The incidence of local and systemic adverse events was higher in those patients with past disease.

APOL1 High-Risk Genotype is Not Associated With New or Worsening of Proteinuria or Kidney Function Decline Following COVID-19 Vaccination

SARS-CoV-2 infection increases systemic inflammatory cytokines which act as a second-hit driver of Apolipoprotein L1 (APOL1)-mediated collapsing glomerulopathy. SARS-CoV-2 vaccination also increases cytokines. Recent reports of new glomerular disease in individuals with APOL1 high-risk genotype (HRG) following SARS-CoV-2 vaccination raised the concern SARS-CoV-2 vaccination may also act as a second-hit driver of APOL1-mediated glomerulopathy. We screened 1507 adults in the Duke's Measurement to Understand Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) registry and enrolled 105 eligible participants with available SARS-CoV-2 vaccination data, prevaccination and postvaccination serum creatinine, and urine protein measurements. Paired data were stratified by number of APOL1 risk alleles (RAs) and compared within groups using Wilcoxon signed rank test and across groups by analysis of variance. Among 105 participants, 30 (28.6%) had 2, 39 (37.1%) had 1, and 36 (34.3%) had 0 APOL1 RA. Most of the participants (94%) received at least 2 doses of vaccine. Most (98%) received the BNT162B2 (Pfizer) or mRNA-1273 (Moderna) vaccine. On average, the prevaccine and postvaccine laboratory samples were drawn 648 days apart. There were no detectable differences between pre- and post-serum creatinine or pre- and post-urine albumin creatinine ratio irrespective of the participants' APOL1 genotype. Finally, most participants with APOL1 RA had the most common haplotype (E150, I228, and K255) and lacked the recently described protective N264K haplotype. In this observational study, APOL1 HRG is not associated with new or worsening of proteinuria or decline in kidney function following SARS-CoV-2 vaccination. Validation of this result in larger cohorts would further support the renal safety of SARS-CoV-2 vaccine in individuals with APOL1 HRG.

The impact of comorbidity status in COVID-19 vaccines effectiveness before and after SARS-CoV-2 omicron variant in northeastern Mexico: a retrospective multi-hospital study.

The end of the coronavirus disease 2019 (COVID-19) pandemic has been declared by the World Health Organization on May 5, 2023. Several vaccines were developed, and new data is being published about their effectiveness. However, the clinical trials for the vaccines were performed before the Omicron variant appeared and there are population groups where vaccine effectiveness still needs to be tested. The overarching goal of the present study was to analyze the effects of COVID-19 vaccination before and after the Omicron variant in patients considering comorbidities in a population from Nuevo Leon, Mexico. Epidemiological COVID-19 data from the Mexican Social Security Institute were collected from 67 hospitals located in northeastern Mexico, from July 2020 to May 2023, and a total of 669,393 cases were compiled, 255,819 reported a SARS-CoV-2 positive reverse transcription quantitative polymerase chain reaction (RT-qPCR) test or a positive COVID-19 antigen rapid test. Before Omicron (BO, 2020-2021), after 14 days of two doses of COVID-19 vaccine, BNT162b2 and ChAdOx1 vaccines were effective against infection in non-comorbid and all comorbid subgroups, whereas after Omicron (AO, 2022- 2023) there was no significant effectiveness against infection with none of the vaccines. Regarding hospitalization BO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 significantly protected non-comorbid patients whereas BNT162b2, ChAdOx1, and mRNA-1273, protected all comorbid subgroups against hospitalization. AO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 were effective against hospitalization in non-comorbid patients whereas for most comorbid subgroups BNT162b2, ChAdOx1 and CoronaVac were effective against hospitalization. Non-comorbid patients were protected against death as an outcome of COVID-19 during the BO period with most vaccines whereas a reduction in effectiveness was observed AO with mRNA-1273 vaccines in patients with hypertension, and diabetes mellitus. BO, COVID-19 vaccines were effective against infection, hospitalization, and death whereas AO, COVID-19 vaccines failed to protect the population from COVID-19 infection. A varying effectiveness against hospitalization and death is observed AO.

Immune response against the SARS-CoV-2 spike protein in cancer patients after COVID-19 vaccination during the Omicron wave: a prospective study

BackgroundCancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. MethodsWe conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). ResultsThe humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments. ConclusionsCancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.

Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases.

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti-spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti-type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.

Immunogenicity of Monovalent mRNA-1273 and BNT162b2 Vaccines in Children

The messenger RNA (mRNA)-based coronavirus disease 2019 vaccines approved for use in children <5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by monovalent mRNA-based coronavirus disease 2019 vaccines in young children. We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected 1 month after primary vaccine series completion for the measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicronsubvariants (BA.1, BA.4/5). Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicronsubvariants. Children with a previous history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicronsubvariants, which is consistent with the occurrence of identified infections during the circulation of Omicronsubvariants in the region. Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses 1 month after vaccination in young children. In addition, previous infection significantly enhanced the strength of antibody responses to Omicronsubvariants. The authors of future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.

Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines.

Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.