RESUMEN
SARS-CoV-2 is a virus which infects the respiratory tract and may cause severe, occasionally life-threatening disease COVID-19. In more than 5% of symptomatic patients the infection is associated with post-acute symptoms. The initial contact of the virus with the immune system of the nasopharynx and oropharynx induces a mucosal immune response manifested by the production of secretory IgA (sIgA) antibodies which may contribute to the restriction of the infection to the upper respiratory tract and an asymptomatic or clinically mild disease. The current systemically administered vaccines protected against the severe COVID-19 infection and its post-acute sequelae. However, they do not induce antibodies in mucosal secretions in SARS-CoV-2-naive individuals. In contrast, in those who previously experienced mucosal infection, systemically administered vaccines may stimulate sIgA production. The clinical benefit of systemic vaccination convincingly documented in tens of millions of individuals overshadows the rare, sometimes controversial reports of complications encountered after vaccination. The inability of current SARS-CoV-2 vaccines to induce mucosal immune responses and to prevent the spreading of the virus by external secretions demonstrates the mutual independence of mucosal and systemic compartments of the immune system, and thus emphasizes need for the development of vaccines inducing protective immune responses in both compartments.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Vacunación , Inmunidad MucosaRESUMEN
Patients undergoing hemodialysis are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, with mortality rates higher than that of the general population. Vaccination reduces the risk of adverse outcomes, with booster doses being particularly beneficial. However, limited data are available on the effectiveness of subsequent vaccinations or their effect on increasing antibody levels. This single-center study aimed to investigate changes in SARS-CoV-2 IgG antibody titers following the fourth vaccination among 28 patients undergoing hemodialysis. Blood tests were conducted at various intervals post-vaccination, with a focus on identifying factors associated with antibody levels. The IgG antibody levels rapidly increased by Day 7 post-vaccination, with a median time to peak of 11 days. Antibody titers tended to be higher in male patients than in female patients. This study sheds light on the immune response to the fourth vaccination in patients undergoing hemodialysis. As this study included a small sample size, with a short observation period, further research is warranted to comprehensively understand the effectiveness of vaccination and the benefits of additional doses of vaccine.
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Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , Diálisis Renal , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Masculino , Femenino , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Persona de Mediana Edad , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Japón/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunación , Anciano de 80 o más Años , Inmunización Secundaria , Adulto , Pueblos del Este de AsiaRESUMEN
Objective: To evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage. Methods: Single-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded. Results: Fifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77-0.98, p=0.022). Larger studies are needed to validate these results. Conclusion: COVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients.
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Vacunas contra la COVID-19 , COVID-19 , Esclerosis Múltiple , Proteínas de Neurofilamentos , SARS-CoV-2 , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/sangre , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/sangre , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Proteínas de Neurofilamentos/sangre , SARS-CoV-2/inmunología , Adulto Joven , Estudios Longitudinales , Biomarcadores/sangre , Axones/patología , España/epidemiología , Vacunación/efectos adversosRESUMEN
BACKGROUND: Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few data on COVID-19 vaccine effectiveness (VE) are available from middle-income countries in the WHO European Region. We evaluated primary series COVID-19 VE against laboratory-confirmed COVID-19 among HCWs in Georgia. METHODS: HCWs in six hospitals in Georgia were invited to enroll in a prospective cohort study conducted during March 19-December 5, 2021. Participants completed weekly symptom questionnaires. Symptomatic HCWs were tested by RT-PCR and/or rapid antigen test (RAT), and participants were routinely tested for SARS-CoV-2 by RT-PCR or RAT, regardless of symptoms. Serology was collected at enrolment, and quarterly thereafter, and tested by electrochemiluminescence immunoassay for SARS-CoV-2 antibodies. We defined primary series vaccination as two doses of COVID-19 vaccine received ≥14 days before symptom onset. We estimated VE as (1-hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying covariate. Estimates were adjusted by potential confounders that changed the VE estimate by more than 5%, according to the change-in-estimate approach. RESULTS: Overall, 1561/3849 (41%) eligible HCWs enrolled and were included in the analysis. The median age was 40 (IQR: 30-53), 1318 (84%) were female, and 1003 (64%) had laboratory evidence of prior SARS-Cov-2 infection. At enrolment, 1300 (83%) were unvaccinated; By study end, 1082 (62%) had completed a primary vaccine series (69% BNT162b2 (Pfizer-BioNTech); 22% BBIBP-CorV (Sinopharm); 9% other). During the study period, 191(12%) participants had a new PCR- or RAT-confirmed symptomatic SARS-CoV-2 infection. VE against PCR- or RAT- confirmed symptomatic SARS-CoV-2 infection was 58% (95%CI: 41; 70) for all primary series vaccinations, 68% (95%CI: 51; 79) for BNT162b2, and 40% (95%CI: 1; 64) for BBIBP-CorV vaccines. Among previously infected HCWs, VE was 58% (95%CI: 11; 80). VE against medically attended COVID-19 was 52% (95%CI: 28; 68), and VE against hospitalization was 69% (95% CI: 36; 85). During the period of predominant Delta variant circulation (July-December 2021), VE against symptomatic COVID-19 was 52% (95%CI: 30; 66). CONCLUSIONS: Primary series vaccination with BNT162b2 and BBIBP-CorV was effective at preventing COVID-19 among HCWs, most of whom had previous infection, during a period of mainly Delta circulation. Our results support the utility of COVID-19 primary vaccine series, and the importance of increasing coverage, even among previously infected individuals.
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Vacunas contra la COVID-19 , COVID-19 , Personal de Salud , SARS-CoV-2 , Eficacia de las Vacunas , Humanos , Femenino , Masculino , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/inmunología , COVID-19/virología , Adulto , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Persona de Mediana Edad , Estudios Prospectivos , Georgia (República)/epidemiología , Vacunación , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificaciónRESUMEN
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored. METHODS: A prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay. RESULTS: Faecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis. CONCLUSIONS: The findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy.
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Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Microbioma Gastrointestinal , Inmunización Secundaria , SARS-CoV-2 , Vacunación , Humanos , Microbioma Gastrointestinal/inmunología , Masculino , Femenino , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Vacuna BNT162/inmunología , Vacunas contra la COVID-19/inmunología , Persona de Mediana Edad , ChAdOx1 nCoV-19/inmunología , Estudios Prospectivos , Formación de Anticuerpos/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Inmunidad Humoral/inmunología , Adulto JovenRESUMEN
During COVID-19 pandemic, cases of postvaccination infections and restored SARS-CoV-2 virus have increased after full vaccination, which might be contributed to by immune surveillance escape or virus rebound. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides were designed based on the well-conserved S2 region of the SARS-CoV-2 spike protein regardless of rapid mutation and glycosylation hindrance. The UC peptides were characterized for its effect on immune molecules and cells by HLA-tetramer refolding assay for HLA-binding ability, by HLA-tetramer specific T cell assay for engaged cytotoxic T lymphocytes (CTLs) involvement, by HLA-dextramer T cell assay for B cell activation, by intracellular cytokine release assay for polarization of immune response, Th1 or Th2. The specific lysis activity assay of T cells was performed for direct activation of cytotoxic T lymphocytes by UC peptides. Mice were immunized for immunogenicity of UC peptides in vivo and immunized sera was assay for complement cytotoxicity assay. Results appeared that through the engagement of UC peptides and immune molecules, HLA-I and II, that CTLs elicited cytotoxic activity by recognizing SARS-CoV-2 spike-bearing cells and preferably secreting Th1 cytokines. The UC peptides also showed immunogenicity and generated a specific antibody in mice by both intramuscular injection and oral delivery without adjuvant formulation. In conclusion, a T-cell vaccine could provide long-lasting protection against SARS-CoV-2 either during reinfection or during SARS-CoV-2 rebound. Due to its ability to eradicate SARS-CoV-2 virus-infected cells, a COVID-19 T-cell vaccine might provide a solution to lower COVID-19 severity and long COVID-19.
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Linfocitos B , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Linfocitos T Citotóxicos , Vacunas de Subunidad , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , Humanos , Ratones , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Linfocitos B/inmunología , Linfocitos T Citotóxicos/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Femenino , Antígenos HLA/inmunología , Ratones Endogámicos BALB C , Vacunas de Subunidades ProteicasRESUMEN
Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2. Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed. Results: Multivariate regression analysis showed anti-cd20 (ß= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (ß=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population. Discussion: Findings regarding humoral and cellular response are consistent with previous reports.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunosupresores , Esclerosis Múltiple , SARS-CoV-2 , Humanos , Masculino , Femenino , Inmunosupresores/uso terapéutico , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/tratamiento farmacológico , COVID-19/inmunología , COVID-19/prevención & control , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Argentina , Adenoviridae/genética , Adenoviridae/inmunología , Inmunidad Humoral , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
In the wake of the novel Coronavirus, it has become imperative to develop vaccines that can alert our immune system to the virus, hence reducing the severity of disease if exposed to it. Different types of vaccines have been studied in this respect, such as nucleic acid vaccines (mRNA and DNA vaccines), vector-based vaccines, whole-virus vaccines (inactivated virus and live-attenuated vaccine), as well as protein subunits vaccines. The results have demonstrated that these vaccines are efficient against both the original strain and emerging variants. Furthermore, they also proved their safety with no grave adverse events. Despite this, hesitancy toward taking these vaccines is still present among certain groups in society due to various factors. Special emphasis has been placed on studies concerning pregnant women, children, elderly people, and immunocompromised individuals where efficacy and safety were proven.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunación , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunación/métodos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Femenino , Embarazo , Huésped Inmunocomprometido , Vacunas de ARNm/inmunologíaRESUMEN
It has been assumed that the COVID-19 vaccination reduces the risk of transmission to others. Results during the delta predominance show that the viral load in the vaccinated population is not consistently lower compared to the unvaccinated, and during the omicron predominance, the viral load was even somewhat higher. Levels of infectious SARS-CoV-2 were partly lower in the vaccinated population. Viral loads were mostly lower in re-infections compared to breakthrough infections. Viral clearance including the detection of infectious virus has mostly been described to be faster in the vaccinated population suggesting a shorter duration as a possible source for transmission. The epidemiological relevance of this finding remains uncertain. Approximately half of the transmission studies found lower secondary attack rates from the fully vaccinated population, but the results are probably best explained by the vaccination status of the contact population. Public health data from the UK show that the number of COVID-19 cases is higher among the fully vaccinated and boosted population who might be possible sources, in contrast to lower case numbers within the first three months among the vaccinated obtained in phase 3 trials on symptomatic cases. Overall, there is no convincing evidence that the COVID-19 vaccination significantly reduces the risk to transmit SARS-CoV-2 to others.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunación , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Vacunación/métodos , Carga ViralRESUMEN
The pandemic caused by the SARS-CoV-2 virus has been ongoing for over three years. After the initial months of confusion and searching for different solutions in the fight against this disease, several different vaccines were developed. Although they were eagerly awaited, social networks were flooded with negative and discouraging comments about vaccines. Citizens' views on this issue varied not only from country to country but also within the same country. At the same time, a certain number of officials in some countries contributed to a negative view of vaccines. Therefore, the first goal of this paper is to review the results of research conducted in different countries and then analyze the results of research conducted in Serbia. The sample consisted of 301 respondents. The results of the research show that the majority of respondents refused to be vaccinated, as they do not believe in the effectiveness or safety of the vaccine against COVID-19, nor do they trust the state authorities in their fight against the pandemic.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunación , Humanos , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Vacunación/psicología , Adulto , Femenino , Persona de Mediana Edad , Serbia , Masculino , Anciano , Opinión Pública , Pandemias/prevención & controlRESUMEN
The advent of COVID-19 has brought the use of computer tools to the fore in health research. In recent years, computational methods have proven to be highly effective in a variety of areas, including genomic surveillance, host range prediction, drug target identification, and vaccine development. They were also instrumental in identifying new antiviral compounds and repurposing existing therapeutics to treat COVID-19. Using computational approaches, researchers have made significant advances in understanding the molecular mechanisms of COVID-19 and have developed several promising drug candidates and vaccines. This chapter highlights the critical importance of computational drug design strategies in elucidating various aspects of COVID-19 and their contribution to advancing global drug design efforts during the pandemic. Ultimately, the use of computing tools will continue to play an essential role in health research, enabling researchers to develop innovative solutions to combat new and emerging diseases.
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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Biología Computacional , Diseño de Fármacos , SARS-CoV-2 , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , COVID-19/virología , COVID-19/epidemiología , SARS-CoV-2/efectos de los fármacos , Biología Computacional/métodos , Pandemias , Reposicionamiento de Medicamentos/métodos , Vacunas contra la COVID-19/uso terapéutico , Vacunas contra la COVID-19/inmunologíaRESUMEN
Sudden sensorineural hearing loss (SSNHL) has emerged as a potential complication of COVID-19 infection and vaccination. Various mechanisms by which the SARS-CoV-2 virus can cause hearing loss have been reported, including direct viral invasion, neuroinflammation, blood flow disturbances, and immune-mediated response. However, the temporal relationship between COVID-19 infection and SSNHL remains unclear, with mixed findings and conflicting results reported in different studies. Similarly, while anecdotal reports have linked COVID-19 vaccination to SSNHL, evidence remains scarce. Establishing a correlation between COVID-19 vaccines and SSNHL implies a complex and multifactorial pathogenesis involving interactions between the immune system and the body's stress response. Nevertheless, it is important to consider the overwhelming evidence of the vaccines' safety and efficacy in limiting the spread of the disease and remains the primordial tool in reducing death.
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Vacunas contra la COVID-19 , COVID-19 , Pérdida Auditiva Súbita , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/complicaciones , Pérdida Auditiva Súbita/etiología , Pérdida Auditiva Súbita/inmunología , Pérdida Auditiva Súbita/virología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Vacunación/efectos adversos , Oído Interno/inmunología , Pérdida Auditiva Sensorineural/virología , Pérdida Auditiva Sensorineural/inmunología , Pérdida Auditiva Sensorineural/etiologíaRESUMEN
In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , COVID-19/inmunología , COVID-19/virología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Femenino , Masculino , Adulto , Eficacia de las VacunasRESUMEN
Introduction: Pre-existent pools of coronavirus-specific or cross-reactive T cells were shown to shape the development of cellular and humoral immune responses after primary mRNA vaccination against SARS-CoV-2. However, the cellular determinants of responses to booster vaccination remain incompletely understood. Therefore, we phenotypically and functionally characterized spike antigen-specific T helper (Th) cells in healthy, immunocompetent individuals and correlated the results with cellular and humoral immune responses to BNT162b2 booster vaccination over a six-month period. Methods: Blood of 30 healthy healthcare workers was collected before, 1, 3, and 6 months after their 3rd BNT162b2 vaccination. Whole blood was stimulated with spike peptides and analyzed using flow cytometry, a 13-plex cytokine assay, and nCounter-based transcriptomics. Results: Spike-specific IgG levels at 1 month after booster vaccination correlated with pre-existing CD154+CD69+IFN-γ+CD4+ effector memory cells as well as spike-induced IL-2 and IL-17A secretion. Early post-booster (1-month) spike IgG levels (r=0.49), spike-induced IL2 (r=0.58), and spike-induced IFNγ release (r=0.43) correlated moderately with their respective long-term (6-month) responses. Sustained robust IgG responses were significantly associated with S-specific (CD69+±CD154+±IFN-γ+) Th-cell frequencies before booster vaccination (p=0.038), especially double/triple-positive type-1 Th cells. Furthermore, spike IgG levels, spike-induced IL2 release, and spike-induced IFNγ release after 6 months were significantly associated with increased IL2 & IL4, IP10 & MCP1, and IFNγ & IP10 levels at 1 month post-booster, respectively. On the transcriptional level, induction of pathways associated with both T-cell proliferation and antigen presentation was indicative of sustained spike-induced cytokine release and spike-specific IgG production 6 months post-booster. Using support vector machine models, pre-booster spike-specific T-cell frequencies and early post-booster cytokine responses predicted sustained (6-month) responses with F1 scores of 0.80-1.00. Discussion: In summary, spike-specific Th cells and T-cellular cytokine signatures present before BNT162b2 booster vaccination shape sustained adaptive cellular and humoral responses post-booster. Functional T-cell assays might facilitate early identification of potential non-responders.
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Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Citocinas , Inmunidad Humoral , Inmunización Secundaria , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Linfocitos T Colaboradores-Inductores , Humanos , Citocinas/metabolismo , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , COVID-19/inmunología , COVID-19/prevención & control , Masculino , SARS-CoV-2/inmunología , Adulto , Femenino , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Linfocitos T Colaboradores-Inductores/inmunología , Vacunas contra la COVID-19/inmunología , Inmunidad Celular , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , VacunaciónRESUMEN
Despite the decrease in mortality and morbidity due to SARS-CoV-2 infection, the incidence of infections due to Omicron subvariants of SARS-CoV-2 remains high. The mutations acquired by these subvariants, mainly concentrated in the receptor-binding domain (RBD), have caused a shift in infectivity and transmissibility, leading to a loss of effectiveness of the first authorized COVID-19 vaccines, among other reasons, by neutralizing antibody evasion. Hence, the generation of new vaccine candidates adapted to Omicron subvariants is of special interest in an effort to overcome this immune evasion. Here, an optimized COVID-19 vaccine candidate, termed MVA-S(3P_BA.1), was developed using a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein from the Omicron BA.1 variant. The immunogenicity and efficacy induced by MVA-S(3P_BA.1) were evaluated in mice in a head-to-head comparison with the previously generated vaccine candidates MVA-S(3P) and MVA-S(3Pbeta), which express prefusion-stabilized S proteins from Wuhan strain and Beta variant, respectively, and with a bivalent vaccine candidate composed of a combination of MVA-S(3P) and MVA-S(3P_BA.1). The results showed that all four vaccine candidates elicited, after a single intramuscular dose, protection of transgenic K18-hACE2 mice challenged with SARS-CoV-2 Omicron BA.1, reducing viral loads, histopathological lesions, and levels of proinflammatory cytokines in the lungs. They also elicited anti-S IgG and neutralizing antibodies against various Omicron subvariants, with MVA-S(3P_BA.1) and the bivalent vaccine candidate inducing higher titers. Additionally, an intranasal immunization in C57BL/6 mice with all four vaccine candidates induced systemic and mucosal S-specific CD4+ and CD8+ T-cell and humoral immune responses, and the bivalent vaccine candidate induced broader immune responses, eliciting antibodies against the ancestral Wuhan strain and different Omicron subvariants. These results highlight the use of MVA as a potent and adaptable vaccine vector against new emerging SARS-CoV-2 variants, as well as the promising feature of combining multivalent MVA vaccine candidates.
Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , Ratones Transgénicos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Ratones , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Humanos , Enzima Convertidora de Angiotensina 2/inmunología , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Femenino , Vacunas de ADN/inmunología , Virus Vaccinia/inmunología , Virus Vaccinia/genética , Inmunogenicidad VacunalRESUMEN
Archaeosomes are liposomes traditionally comprised of total polar lipids or semi-synthetic glycerolipids of ether-linked isoprenoid phytanyl cores with varied glycol- and amino-head groups. We have developed a semi-synthetic archaeosome formulation based on sulfated lactosylarchaeol (SLA) that can be readily synthesized and easily formulated to induce robust humoral and cell-mediated immunity following systemic immunization, enhancing protection in models of infectious disease and cancer. Liposomes composed of SLA have been shown to be a safe and effective vaccine adjuvant to a multitude of antigens in preclinical studies including hepatitis C virus E1/E2 glycoproteins, hepatitis B surface antigen, influenza hemagglutinin, Rabbit Hemorrhagic Disease Virus antigens, and SARS-CoV-2 Spike antigens based on the ancestral strain as well as multiple variants of concern. With the COVID-19 pandemic highlighting the need for new vaccine technologies including adjuvants, this review outlines the studies conducted to date to support the development of SLA archaeosomes as a vaccine adjuvant.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Liposomas , Humanos , Animales , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Adyuvantes de Vacunas , SARS-CoV-2/inmunología , Éteres de Glicerilo , Adyuvantes Inmunológicos/administración & dosificación , Glucolípidos/inmunología , Glucolípidos/químicaRESUMEN
In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS-CoV-2. This study investigated the development of broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through the "Knob-into-Hole" technique. We constructed various recombinant proteins incorporating the receptor-binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS-CoV-2 with those of SARS-CoV or MERS-CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD and MERS_D614G/BA.1_XBB.1.5-RBD, elicited remarkable breadth and potency in neutralizing all known SARS-CoV-2 variants, SARS-CoV, related sarbecoviruses like GD-Pangolin and WIV1, and even MERS-CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Coronavirus del Síndrome Respiratorio de Oriente Medio , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Ratones , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , Vacunas contra la COVID-19/inmunología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Fragmentos Fc de Inmunoglobulinas/inmunología , Fragmentos Fc de Inmunoglobulinas/genética , Fragmentos Fc de Inmunoglobulinas/química , COVID-19/prevención & control , COVID-19/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Ratones Endogámicos BALB C , Femenino , Dominios Proteicos , Pruebas de Neutralización , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genéticaRESUMEN
Due to the persisting development of SARS-CoV-2 variants, studies on the kinetics, duration, and function of antibodies are essential for vaccine development and long-term immunity prediction. This longitudinal study examined post-vaccination antibody responses in people after receiving CoronaVac or ChAdOx1 vaccines with or without a history of SARS-CoV-2 infection. Conducted in Indonesia between August 2021 and May 2023, this study involved 121 participants divided into two groups based on the received vaccine types and monitored for 18 months post-second dose vaccination by assessing the binding antibody (BAb) level and neutralizing antibody (NAb) inhibition rate at six time points. The study also documented the participants' age, gender, and body mass index (BMI). Before the first dose vaccination, 85 (70.2%) participants were reactive BAb (defined by BAb level ≥50 AU/mL) indicating a history of infection. In the CoronaVac group, only 53.1% were reactive BAb. However, 100% of participants were positive NAb (defined by NAb inhibition rate ≥30%), which indicates a past history of infection with low initial or rapidly decreasing BAb levels. In the ChAdOx1 group, 81.9% of participants were reactive, while only 54.2% were positive NAb, suggesting a recent infection with a high BAb level but a relatively low NAb inhibition rate. During the 18 months post-second dose vaccination, the BAb levels fluctuated. However, 100% of participants were positive NAb. No significant difference in antibody response was documented among participants with or without infection history. Also, no significant impact was presented by the factors of sex, age, and BMI. The findings highlight the crucial of the vaccine in public health and how vaccination strategies could be optimized effectively during and after the post-pandemic.