Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers.

BACKGROUND: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. METHODS: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. FINDINGS: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. INTERPRETATION: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. FUNDING: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.

Comparison of antibody responses after the 1st and 2nd doses of COVID-19 vaccine with those of patients with mild or severe COVID-19.

BACKGROUND/AIMS: Data comparing the antibody responses of different coronavirus disease 2019 (COVID-19) vaccine platforms according to dose with natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced antibody responses are limited. METHODS: Blood samples from adult patients with mild and severe COVID-19 and healthcare workers who received ChAdOx1 nCoV-19 vaccine (2nd dose at 12-week intervals) and BNT162b2 vaccine (2nd dose at 3-week intervals) were collected and compared by immunoglobulin G immune responses to SARS-CoV-2 specific spike protein using an in-house-developed enzyme-linked immunosorbent assay. RESULTS: A total of 53 patients, including 12 and 41 with mild and severe COVID-19, respectively, were analyzed. In addition, a total of 73 healthcare workers, including 37 who received ChAdOx1 nCoV-19 and 36 who received BNT162b2, were enrolled. Antibody responses after the first and second doses of the ChAdOx1 nCoV-19 vaccine or the first dose of the BNT162b2 vaccine were similar to those in convalescent patients with mild COVID-19, but lower than those in convalescent patients with severe COVID-19, respectively. However, after the second dose of the BNT162b2 vaccine, the antibody response was comparable to that in convalescent patients with severe COVID-19. CONCLUSION: Our data suggest that the second dose of mRNA vaccination may be more beneficial in terms of long-term immunity and prevention of SARS-CoV-2 variant infection than a single dose of COVID-19 vaccination or homologous second challenge ChAdOx1 nCoV-19.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID-19 vaccine in haemato-oncological patients with no antibody response.

Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.

An analysis of antibody responses and clinical sequalae of the Sinopharm HB02 COVID19 vaccine in dialysis patients in the United Arab Emirates.

AIM: To establish the responses to the Sinopharm HB02 COVID-19 vaccination in the dialysis population, which are not well established. We examined the humoral responses to the Sinopharm COVID vaccine in haemodialysis patients. METHODS: Standard vaccinations (two doses at interval of ~21 days) were given to all consenting haemodialysis patients on dialysis (n = 1296). We measured the antibody responses at 14-21 days after the second vaccine to define the development of anti-spike antibodies >15 AU/ml after vaccination and observed the clinical effects of vaccination. RESULTS: Vaccination was very well tolerated with few side-effects. In those who consented to antibody measurements, (n = 446) baseline sampling showed 77 had positive antibodies, yet received full vaccination without any apparent adverse events. Positive anti-spike antibodies developed in 50% of the 270 baseline negative patients who had full sampling, compared with 78.1% in the general population. COVID infection continues to occur in both vaccinated and unvaccinated individuals, but in the whole group vaccination appears to have been associated with a reduction in the case fatality rate. CONCLUSION: The humoral immune responses to standard HB02 vaccination schedules are attenuated in a haemodialysis cohort, but likely the vaccine saves lives. We suggest that an enhanced HB02 vaccination course or antibody checking may be prudent to protect this vulnerable group of patients. We suggest a booster dose of this vaccine at 3 months should be given to all dialysis patients, on the grounds that it is well tolerated even in those with good antibody levels and there may be a survival advantage.

Role of interleukin-6 in antigen-specific mucosal immunoglobulin A induction by cationic liposomes.

The COVID-19 pandemic, caused by a highly virulent and transmissible pathogen, has proven to be devastating to society. Mucosal vaccines that can induce antigen-specific immune responses in both the systemic and mucosal compartments are considered an effective measure to overcome infectious diseases caused by pathogenic microbes. We have recently developed a nasal vaccine system using cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and cholesteryl 3ß-N-(dimethylaminoethyl)carbamate in mice. However, the comprehensive molecular mechanism(s), especially the host soluble mediator involved in this process, by which cationic liposomes promote antigen-specific mucosal immune responses, remain to be elucidated. Herein, we show that intranasal administration of cationic liposomes elicited interleukin-6 (IL-6) expression at the site of administration. Additionally, both nasal passages and splenocytes from mice nasally immunized with cationic liposomes plus ovalbumin (OVA) were polarized to produce IL-6 when re-stimulated with OVA in vitro. Furthermore, pretreatment with anti-IL-6R antibody, which blocks the biological activities of IL-6, attenuated the production of OVA-specific nasal immunoglobulin A (IgA) but not OVA-specific serum immunoglobulin G (IgG) responses. In this study, we demonstrated that IL-6, exerted by nasally administered cationic liposomes, plays a crucial role in antigen-specific IgA induction.

Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.

BACKGROUND: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. METHODS: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression. FINDINGS: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128-317), p < 0·001), fingolimod (26-fold decrease (95%CI=16-42), p < 0·001) and rituximab (20-fold decrease (95%CI=10-43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46-4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days). INTERPRETATION: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. FUNDING: FISM[2021/Special-Multi/001]; Italian Ministry of Health'Progetto Z844A 5 × 1000'.

Production and persistence of specific antibodies in COVID-19 patients with hematologic malignancies: role of rituximab.

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

Analysis of antibody responses after COVID-19 vaccination in liver transplant recipients and those with chronic liver diseases.

BACKGROUND & AIMS: Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials studying the efficacy of vaccines against SARS-CoV-2. Although the clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown, many societies have recommended vaccination of this highly vulnerable patient population. METHODS: In this prospective study, we determined antibody responses to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver disease (CLD) with and without cirrhosis. RESULTS: Of the 233 patients enrolled so far, 62 were LT recipients, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Antibody titers were defined as undetectable (<0.40 U/ml), suboptimal (0.40-250 U/ml) and adequate (>250 U/ml). Of the 62 patients who had LT, antibody levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47-212 U/ml) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable antibody levels and 15 had suboptimal (median titer 41.3, range 0.49-221 U/L) antibody responses. Of the 92 patients without cirrhosis, 4 had undetectable antibody levels and 19 had suboptimal (median titer 95.5, range 4.9-234 U/L) antibody responses. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of the Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. CONCLUSIONS: Poor antibody responses after SARS-CoV-2 vaccination were seen in 61% of LT recipients and 24% of those with CLD. LAY SUMMARY: The clinical efficacy of COVID-19 vaccines in immunocompromised patients is unknown. We performed a prospective study to evaluate immune responses to COVID-19 vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 patients with cirrhosis and 92 with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody responses (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody responses when adjusted for other factors.

Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity.

Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab) responses. However, it fails to induce secretory immunoglobulin (Ig) A (SIgA) in mucosal tissues and is poor in inducing Th1 and cell-mediated immunity. Alum stimulates interleukin 1 (IL-1) and the recruitment of myeloid cells, including neutrophils. We investigated whether neutrophil elastase regulates the adjuvanticity of alum, and whether a strategy targeting neutrophil elastase could improve responses to injected vaccines. Mice coadministered a pharmacological inhibitor of elastase, or lacking elastase, developed high-affinity serum IgG and IgA antibodies after immunization with alum-adsorbed protein vaccines, including the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). These mice also developed broader antigen-specific CD4+ T cell responses, including high Th1 and T follicular helper (Tfh) responses. Interestingly, in the absence of elastase activity, mucosal SIgA responses were induced after systemic immunization with alum as adjuvant. Importantly, lack or suppression of elastase activity enhanced the magnitude of anti-SARS-CoV-2 spike subunit 1 (S1) antibodies, and these antibodies reacted with the same epitopes of spike 1 protein as sera from COVID-19 patients. Therefore, suppression of neutrophil elastase could represent an attractive strategy for improving the efficacy of alum-based injected vaccines for the induction of broad immunity, including mucosal immunity.

Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients.

Haemato-oncological patients are at risk in case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Currently, vaccination is the best-evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato-oncological patients. A total of 259 haemato-oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti-SARS-CoV-2-S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2-fold increased risk of non-responding (95% confidence interval 3·2-63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non-response. Low immunoglobulin G (IgG) level, lymphocyte- and natural killer (NK)-cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side-effects. Patients with side-effects developed a higher S/RBD-antibody titre compared to patients without side-effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non-response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non-response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato-oncological patients.

Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (CLL) is associated with immunosuppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination. We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 286 patients underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine (n = 267) compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine (n = 55), compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine. This work supports the need for optimisation of vaccination strategy in patients with CLL including the potential utility of booster vaccines.

One dose of SARS-CoV-2 vaccine exponentially increases antibodies in individuals who have recovered from symptomatic COVID-19.

BACKGROUNDThe COVID-19 vaccines currently in use require 2 doses to achieve optimal protection. Currently, there is no indication as to whether individuals who have been exposed to SARS-CoV-2 should be vaccinated, or whether they should receive 1 or 2 vaccine doses.METHODSWe tested the antibody response developed after administration of the Pfizer/BioNTech vaccine in 124 health care professionals, of whom 57 had a previous history of SARS-CoV-2 exposure with or without symptoms.RESULTSPostvaccine antibodies in SARS-CoV-2-exposed individuals increased exponentially within 5 to 18 days after the first dose compared to naive subjects (P < 0.0001). In a multivariate linear regression (LR) model we showed that the antibody response depended on the IgG prevaccine titer and on the exposure to SARS-CoV-2. In symptomatic SARS-CoV-2-exposed individuals, IgG reached a plateau after the second dose, and those who voluntarily refrained from receiving the second dose (n = 7) retained their antibody response. Gastrointestinal symptoms, muscle pain, and fever markedly positively correlated with increased IgG responses. By contrast, all asymptomatic/paucisymptomatic and unexposed individuals showed an important increase after the second dose.CONCLUSIONOne vaccine dose is sufficient in symptomatic SARS-CoV-2-exposed subjects to reach a high titer of antibodies, suggesting no need for a second dose, particularly in light of current vaccine shortage.TRIAL REGISTRATIONClinicalTrials.gov NCT04387929.FUNDINGDolce & Gabbana and the Italian Ministry of Health (Ricerca corrente).

[Vaccination against SARS-CoV-2 in patients with multiple sclerosis]. / Vacunación frente al SARS-CoV-2 en pacientes con esclerosis múltiple.

INTRODUCTION: The recent availability of SARS-CoV-2 vaccines has raised concerns in certain patient groups, such as those with multiple sclerosis. However, there are currently few publications that provide information on this issue. We pooled the information available on the safety and efficacy of vaccination against SARS-CoV-2 in patients with multiple sclerosis, with and without disease-modifying therapy. DEVELOPMENT: The study consisted in a literature search focused on the types of SARS-CoV-2 vaccines, the current status of their approval, and the data available on the safety and efficacy of vaccines in patients with multiple sclerosis, including the new COVID-19 vaccines. Based on this search, the document has been designed taking into account current evidence and expert recommendations. There are no data on the safety and efficacy of SARS-CoV-2 vaccines in patients with multiple sclerosis. However, evidence does exist to suggest that messenger RNA (mRNA) vaccines against SARS-CoV-2 are as safe in these patients as in other individuals. Some therapies with immunosuppressants might reduce the effectiveness of these vaccines and require the scheduling of their administration, preferably before the start of treatment if possible. CONCLUSION: The data available make it possible to recommend mRNA vaccines against SARS-CoV-2 in patients with multiple sclerosis. In patients on fingolimod, cladribine, alemtuzumab, ocrelizumab and rituximab, vaccination prior to the initiation of medication administration would be recommendable whenever possible.

TITLE: Vacunación frente al SARS-CoV-2 en pacientes con esclerosis múltiple.Introducción. La reciente disponibilidad de vacunas contra el SARS-CoV-2 ha suscitado dudas en determinados colectivos de pacientes, como los que padecen esclerosis múltiple. Sin embargo, en la actualidad hay pocas publicaciones que ofrezcan información en este sentido. Se recopila la información disponible sobre la seguridad y la eficacia de la vacunación contra el SARS-CoV-2 en pacientes con esclerosis múltiple, con y sin tratamiento modificador de la enfermedad. Desarrollo. Búsqueda bibliográfica enfocada en los tipos de vacunas contra el SARS-CoV-2, la situación actual de su aprobación, y los datos disponibles sobre la eficacia y la seguridad de las vacunas en pacientes con esclerosis múltiple, incluidas las nuevas vacunas frente a la COVID-19. A partir de esta búsqueda, se ha diseñado el documento recogiendo la evidencia actual y las recomendaciones de expertos. No existen datos sobre la seguridad y la eficacia de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple. Sin embargo, los datos disponibles permiten prever que las vacunas de tipo ARN mensajero (ARNm) frente al SARS-CoV-2 son tan seguras en ellos como en el resto de los individuos. Algunos de los tratamientos inmunosupresores podrían reducir la efectividad de las vacunas y requerir la planificación del momento de su administración, preferentemente antes del inicio del tratamiento en caso de ser posible. Conclusión. Los datos disponibles permiten recomendar las vacunas de tipo ARNm frente al SARS-CoV-2 en los pacientes con esclerosis múltiple. En los pacientes con fingolimod, cladribina, alemtuzumab, ocrelizumab y rituximab, sería recomendable la vacunación previa al inicio de la medicación cuando sea posible.