Evaluation of the humoral immunity in mice induced by foot-and-mouth disease virus-like particles-ZIF-8 complexes with different sizes / 生物工程学报

To further enhance the immune effect of the foot-and-mouth disease (FMD) virus-like particles (VLPs) vaccine, this study prepared FMDV VLPs-zeolitic imidazolate (framework-8, ZIF-8) complexes with different particle sizes. We used a biomimetic mineralization method with Zn2+ and 2-methylimidazole in different concentration ratios to investigate the effect of size on the immunization effect. The results showed that FMDV VLPs-ZIF-8 with three different sizes were successfully prepared, with an approximate size of 70 nm, 100 nm, and 1 000 nm, respectively. Cytotoxicity and animal toxicity tests showed that all three complexes exhibited excellent biological safety. Immunization tests in mice showed that all three complexes enhanced the titers of neutralizing and specific antibodies, and their immune effects improved as the size of the complexes decreased. This study showed that ZIF-8 encapsulation of FMDV VLPs significantly enhanced their immunogenic effect in a size-dependent manner.

Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.@*METHODS@#Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.@*RESULTS@#In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.@*CONCLUSIONS@#Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

Safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use in healthy people aged 9-65 years / 中华预防医学杂志

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.

Research Progress in Antibody Responses Against SARS-CoV-2 Variants of Concern / 中国医学科学院学报

So far,the coronavirus disease 2019(COVID-19)has been persisting for nearly three years,infecting about 700 million people and causing more than 6 million deaths,which has seriously affected the human society.According to Global Initiative on Sharing All Influenza Data,there are more than 12 million SARS-CoV-2 variants,of which the five major variants of concern are Alpha,Beta,Gamma,Delta and Omicron.Their infectivity,pathogencity,and neutralization resistance have changed greatly compared with the original strain,which has brought great pressure to the prevention and control of the pandemic.Antibody level testing is critical for confirming infection,epidemiological investigation,vaccine development,and neutralizing drug preparation.Focusing on the humoral immunity against SARS-CoV-2,this paper introduces the mutation sites,neutralization resistance,and vaccination efficacy of the five variants of concern,and briefly summarizes the evolutionary characteristics,future mutation directions,and host immunity.

Preparation and immunogenicity evaluation of mRNA vaccine against porcine epidemic diarrhea / 生物工程学报

Porcine epidemic diarrhea (PED) is a highly contagious disease that causes high mortality in suckling piglets. Although several licensed inactivated and live attenuated vaccines were widely used, the infection rate remains high due to unsatisfactory protective efficacy. In this study, mRNA vaccine candidates against PED were prepared, and their immunogenicity was evaluated in mice and pregnant sows. The mRNA PED vaccine based on heterodimer of viral receptor binding region (RBD) showed good immunogenicity. It elicited robust humoral and cellular immune responses in mice, and the neutralizing antibody titer reached 1:300 after a single vaccination. Furthermore, it induced neutralizing antibody level similar to that of the inactivated vaccine in pregnant sows. This study developed a new design of PED vaccine based on the mRNA-RBD strategy and demonstrated the potential for clinical application.

Neutralizing Antibody Responses against Five SARS-CoV-2 Variants and T Lymphocyte Change after Vaccine Breakthrough Infections from the SARS-CoV-2 Omicron BA.1 Variant in Tianjin, China: A Prospective Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.@*METHODS@#Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.@*RESULTS@#The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.@*CONCLUSION@#Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.

Detection of neutralizing antibodies among health care workers and staff fully-vaccinated against COVID-19 in a Baguio City tertiary hospital: A cross-sectional study

Background@#Coronavirus disease 2019, otherwise known as COVID-19 is caused by the novel coronavirus. The WHO stated that as of April 24, 2020, no study has evaluated if the antibodies against COVID-19 confer immunity. The aim therefore of this research is to determine the presence of neutralizing antibodies among fully vaccinated Health Care workers and staff of Notre Dame de Chartres Hospital.@*Methods@#This study is a single-center, cross-sectional study conducted at Notre Dame de Chartres Hospital in Baguio City. This study was designed to determine the presence of neutralizing antibodies 6 months after the 2nd dose of COVID-19 vaccine, either with Sinovac (CoronaVac®), an inactivated virus, or Oxford AstraZeneca, a non-replicating viral vector. The study was approved by the Ethics Review Board of the Baguio General Hospital Medical Center. A total of 206 participants enrolled voluntarily in the study. Descriptive statistics such as frequency and percentage were used to determine the baseline characteristics of the research participants. The mean amounts of antibodies after vaccination against COVID-19 were determined. Independent-sample t-test was utilized to determine if there was a significant difference in antibody production when comparing the two brands of vaccine, according to sex, employee status, presence of at least one comorbidity, and history of COVID-19 vaccination. One-way analysis of variance (ANOVA) was used for the variable age. All statistical tests were conducted at p<0.05 level of significance. Computations were done using SPSS version 22.0.@*Results@#A total of 236 healthcare workers and staff of Notre Dame de Chartres Hospital were included in the study. Among the study participants given either Sinovac or AstraZeneca, 52.97% belong to the 20-30 years old age group. Most of them were females (69.92%). For employment status, healthcare workers comprised the majority of the study population at 71.61% while the rest (28.36%) were hospital staff. Most did not have any comorbidities, while 26.27% reported having comorbidities, with hypertension and asthma identified as the predominant diseases at 9.75% and 9.32%, respectively; followed by allergic rhinitis (5.32%) and diabetes mellitus (2.97%). Among the participants, 74.6% were never diagnosed with COVID-19, while 25.4% reported to have been infected, with 16.5% having only mild symptoms. Most of the study participants (67.4%) were inoculated with Sinovac® while the rest (32.6%) received AstraZeneca.@*Conclusion@#There was no significant difference in the mean amount of antibodies when grouped according to each of the following variables: age, sex, employee status, and comorbidities. These results apply to both SINOVAC and AstraZeneca groups. There was a significantly higher mean amount of antibodies in those who had previously contracted COVID-19 than in those who never had a previous infection. On the other hand, comparing the mean amount of antibodies between the two brands of vaccines, SinovacTM and AstraZenecaTM, those who were vaccinated with AstraZenecaTM developed higher amounts of antibodies than those who were vaccinated with SinovacTM.

Altered expression of 15-hydroxyprostaglandin dehydrogenase in chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the expression level and regulatory mechanism of 15-hydroxyprostaglandin dehydrogenase（HPGD） in chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:The expression pattern and level of HPGD in CRSwNP and control was observed using immunofluorescence, and western blot was used for analysis of HPGD expression in nasal polyp tissues. The effect of recombinant human high mobility group box-1（HMGB1） on HPGD expression in primary human nasal epithelial cells was observed, and the potential blocking effect of RAGE neutralizing antibody on HMGB1-induced HPGD expression was investigated. Results:The expression of HPGD was elevated in CRSwNP patients compared to the control, while the protein mainly localized at CD68-positive cells and epithelial cells. Recombinant human HMGB1 stimulated an increase in HPGD expression in primary human nasal mucosal epithelial cells at a time-dependent manner. Additionally, increased phosphorylation levels of MEK and elevated RAGE expression were also observed at 12 hours, but decreased at 24 hours after the incubation of HMGB1. The increase in the expression of HPGD induced by HMGB1 in primary human nasal epithelial cells was partly inhibited with RAGE neutralizing antibody. Conclusion:Elevated HPGD expression is observed in CRSwNP, predominantly in macrophages and epithelial cells. HMGB1 regulates HPGD expression through the RAGE-MEK signaling pathway, potentially providing a new target for future regulation of PGE2levels in CRSwNP.

Passive antibody therapy in emerging infectious diseases / 医学前沿

The epidemic of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern (VOCs) has been ongoing for over 3 years. Antibody therapies encompassing convalescent plasma, hyperimmunoglobulin, and neutralizing monoclonal antibodies (mAbs) applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment. In this review, the development path, action mechanism, clinical research results, challenges, and safety profile associated with the use of COVID-19 convalescent plasma, hyperimmunoglobulin, and mAbs were summarized. In addition, the prospects of applying antibody therapy against VOCs was assessed, offering insights into the coping strategies for facing new infectious disease outbreaks.

Longitudinal proteomic investigation of COVID-19 vaccination

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.

Oral administration of Bifidobacterium breve improves anti-angiogenic drugs-derived oral mucosal wound healing impairment via upregulation of interleukin-10 / 国际口腔科学杂志·英文版

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.

A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9 / 中华医学杂志(英文版)

BACKGROUND@#The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.@*METHODS@#H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.@*RESULTS@#The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.@*CONCLUSION@#The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

Study of three kinds of primary immunization schedules with poliovirus vaccine / 中华预防医学杂志

Objective: To compare the immunogenicity of three kinds immunization programs with poliovirus vaccine. Methods: Healthy infants aged 2 months or over were selected and divided into three groups by complete randomization method. Basic immunization with Sabin inactivated poliovirus vaccine(sIPV) and bivalent oral poliovirus vaccine(bOPV) were completed. Three kinds of basic immunization procedures were 1sIPV+2bOPV,2sIPV+1bOPV and 3sIPV, respectively.Two qualified serums that before basic immunization and 28-42 days later were collected, and measured the poliovirus neutralizing antibody with microcell neutralization method. To compare the difference by analysis of variance, rank test and χ2 test. Results: After the basic immunization, 205 subjects of the positive conversion rate of poliovirus neutralizing antibodies of types Ⅰ, Ⅱ and Ⅲwere all higher than 97.00%, and the positive rates were all higher than 98.00%, the geometric mean titer (GMT) of neutralizing antibody was significantly higher than that before basic immunization in three groups.There were significant differences in the positive rate and GMT before and after basic immunization of typeⅠ, Ⅱand Ⅲ in the three (P<0.05). The highest GMT in three groups after basic immunization were all typeⅠ, followed by type Ⅲ, and the lowest in type Ⅱ. The GMT of type Ⅱin 2sIPV+1bOPV and 3sIPV groups were both higher than that in sIPV+2bOPV group. Conclution: After three kinds of basic immunization, the poliovirus neutralizing antibodies of serum were all at high levels in three groups, which could form an effective immune barrier against poliovirus. The immunogenicity of three kinds of basic immunization programs were all well, but there were certain differences of neutralizing antibodies among three kinds basic immunization programs. The immunogenicity in 2sIPV+1bOPV and 3sIPV groups against typeⅡpoliovirus were better than that in 1sIPV+2bOPV group.

The affinity maturation, characteristics and application of HIV-1 broadly neutralizing antibodies / 中华预防医学杂志

Hundreds of broadly neutralizing antibodies(bNAbs) were successfully isolated from long-term nonprogression(LTNP) of human immunodeficiency virus type 1(HIV-1) infected individuals. Some bNAbs were illustrated could reduce the viral load and the risk of HIV-1 infection. Today, HIV-1 bNAbs are at the center of vaccine development and passive immunization treatment. Usually, the activity of neutralizing antibodies depends on the epitope. The affinity of neutralizing antibodies also plays a vital role in its inhibitory effect. Multiple affinity maturation in vivo actually provides the broad and potent neutralizing activity of HIV-1 bNAbs. When high affinity HIV-1 bNAbs applied in clinic, it can help immune system to remove virus with lower dosage and fewer side effect. While affinity maturation, HIV-1 bNAbs shows unique characteristics, such as extensive of somatic hypermutation(SHM), in-frame insertion and deletion and long CDR 3 region of heavy chain. The key points in the progress that HIV-1 bNAbs affinity maturation will help us understand the relationship between antibodies neutralizing capability and its characteristics.It also potentially provide a reference to design effective HIV-1 immunogen.

Early assessment of the safety and immunogenicity of a third dose (booster) of COVID-19 immunization in Chinese adults / 医学前沿

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.

Elevacion de anticuerpos neutralizantes contra sars cov-2 post vacunacion con sinopharm y astrazeneca hasta la tercera dosis, en el personal del banco de sangre materno infantil cns la paz - bolivia / Elevation of neutralizing antibodies against SARS CoV-2 after vaccination with Sinopharm and AstraZeneca up to the third dose, in the staff of the Maternal and Child Blood Bank CNS La Paz - Bolivia

Introducción: Después de la COVID-19, surgieron luego de muchas investigaciones un suministro de vacunas aprobadas a nivel mundial, dichas vacunas deben conferir una protección eficaz por un tiempo prolongado, poseer un buen perfil de seguridad, ser asequible y ser fácilmente accesible para todos, un reto difícil de conseguir por el tiempo y las características del virus. Objetivo: determinar la concentración de anticuerpos neutralizantes (A. N.) post vacunación en una población de trabajadores del Banco de Sangre Material y métodos: Se realizó un estudio prospectivo, descriptivo, transversal, tomando como población de estudio a todo el personal del Banco de Sangre, varones y mujeres con un rango de edad entre 26 y 72 años, se evaluó el aumento de A. N. después de inoculada la segunda dosis de Sinopharm en fecha 19/05/21, luego se midió la cantidad de anticuerpos generados en fecha 20/10/21 previo a la tercera dosis de refuerzo de Astrazeneca, evaluando nuevamente a los 35 días luego de la tercera dosis 02/12/2021 para finalmente evaluar estos niveles en fecha 26/01/2022. La técnica utilizada fue (ELISA) de la marca EUROIMMUN Anti-SARS- CoV-2 S1 del tipo IgG. Resultados y conclusiones: Se puede verificar que la concentración de A. N. producidos por la vacunación desde Sinopharm y el refuerzo con Astrazeneca favoreció a que dichos anticuerpos se mantengan altos en el tiempo (322 días luego de la primera dosis) llegando a un 80% de la concentración máxima en la lectura final. Concluimos que con cada refuerzo de vacuna anti SARS-CoV-2 el título de A.N. sube de manera significativa, motivo por el cual consideramos importante en nuestro pais una cuarta dosis como método preventivo y de inmunidad.

Introduction: After COVID-19, emerged after much research a supply of vaccines approved worldwide, these vaccines must confer effective protection for a prolonged time, possess a good safety profile, be affordable and be easily accessible to all, a challenge difficult to achieve due to the time and characteristics of the virus. Objective: to determine the concentration of neutralizing antibodies post vaccination in a population of Blood Bank workers; Material and methods: A prospective, descriptive, observational, cross-sectional study was carried out, taking as study population all the Blood Bank personnel, among men and women with an age range between 26 and 72 years old. the increase of Neutralizing Antibodies was evaluated after inoculation of the second dose of Sinopharm on 05/19/21, then the amount of antibodies generated was measured on 10/20/21 prior to the third booster dose of Astrazeneca, evaluating again 35 days after the third dose on 12/02/2021 and finally evaluating these levels on 01/26/2022. The technique used was the EUROIMMUN Anti-SARS-CoV-2 S1 ELISA. Results and conclusions: It can be verified that the concentration of N.A. produced by vaccination from Sinopharm and the booster with Astrazeneca favored that these antibodies remained high over time (322 days after the first dose) reaching 80% of the maximum concentration in the final reading. We conclude that with each booster of anti SARS CoV 2 vaccine, the titer of N.A. rises significantly, which is why we consider important in our country a fourth dose as a preventive and immunity method.

Respuesta humoral inducida por la vacuna BBIBP-CorV/Sinopharm COVID-19 en trabajadores de primera línea / BBIBP-CorV/Sinopharm COVID-19 vaccine-induced humoral response in frontline workers

Con la llegada de la vacuna contra el COVID-19 se evidenció la disminución de casos de Infección por SARS-CoV-2. El objetivo del estudio fue cuantificar la producción de anticuerpos neutralizantes (An) e inmunoglobulina G (S-IgG) en trabajadores de primera línea inmunizados con dos dosis de la vacuna BBIBP-CorV/Sinopharma. Se realizó un estudio observacional analítico transversal en personal de salud inmunizado con la vacuna inactivada (BBIBP-CorV). Sus muestras sanguíneas se recogieron tres meses después de la segunda dosis, para medir las respuestas de anticuerpos (An, S-IgG). De un total de 172 personas evaluadas, 110 (64%) personas ya habían tenido COVID-19 antes de ingresar al estudio, los títulos de An fueron superiores a 10 AU/mL en el 60,5% de los vacunados y el 89,3% mostró S-IgG superior a 50 UA/mL. Los trabajadores mayores de 60 años fueron el grupo que no desarrolló suficientes anticuerpos. La correlación de An y S-IgG fue positiva (r=0,84) (p<0,001). La administración de dos dosis de la vacuna inactivada BBIBP-CorV/Sinopharma provocó una notable respuesta An y S-IgG, excepto en mayores de 60 años(AU)

With the arrival of the vaccine against COVID-19, the decrease in cases of SARS-CoV-2 infection was evidenced. The objective of the study was to quantify the production of neutralizing antibodies (An) and immunoglobulin G (S-IgG) in frontline workers immunized with two doses of the BBIBP-CorV/Sinopharma vaccine. A cross-sectional analytical observational study was carried out in health personnel immunized with the inactivated vaccine (BBIBP-CorV). Their blood samples were collected three months after the second dose, to measure antibody responses (An, S-IgG). Of a total of 172 people evaluated, 110 (64%) people already had COVID-19 before entering the study, An titers were greater than 10 AU/mL in 60.5% of those vaccinated and 89, 3% showed S-IgG greater than 50 AU/mL. Workers older than 60 years were the group that did not develop enough antibodies. The correlation of An and S-IgG was positive (r=0.84) (p<0.001). The administration of two doses of the inactivated BBIBP-CorV/Sinopharma vaccine caused a notable An and S-IgG response, except in those over 60 years of age(AU)

Immune characterization of a Colombian family cluster with SARS-CoV-2 infection / Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2

Abstract | Introduction: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARS- CoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited. Objective: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin. Conclusion: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.

Resumen | Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección. Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2. Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa. Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56 bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia. Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia.

COVID-T: una plataforma funcional para monitorear la respuesta de linfocitos t específicos de SARS-COV-2 en individuos vacunados y recuperados de COVID-19 / COVID-T: A functional platform to monitor SARS-CoV-2-specific T cell responses in vaccinated individuals and COVID-19 recovered patients

Resumen La rápida propagación del coronavirus SARS-CoV-2, agente causal de la enfermedad pandémica emergente COVID-19 y sus nuevas variantes, requiere del compromiso de la comunidad inmunológica para comprender la magnitud y naturaleza de la respuesta inmunológica adaptativa desarrollada por pacientes recuperados de COVID-19 e individuos vacunados con diferentes estrategias y protocolos, a los fines de imple mentar nuevas políticas sanitarias. En la actualidad, la determinación de la inmunidad contra SARS-CoV-2 se basa principalmente en la detección de anticuerpos específicos y la determinación de su actividad neutralizante. Sin embargo, a pesar de la alta sensibilidad de estos ensayos, un número considerable de pacientes e indivi duos vacunados carecen de respuesta humoral detectable, o evidencian una disminución rápida de la misma en el tiempo. Con el objetivo de estudiar la respuesta inmune celular desencadenada frente a SARS-CoV-2, en nuestro laboratorio desarrollamos la "Plataforma COVID-T" estrategia integral optimizada dirigida a caracte rizar y monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 a partir de muestras de sangre de individuos vacunados y/o recuperados de COVID-19. Esta plataforma permite evaluar la naturaleza, magnitud y persistencia de la inmunidad celular T generada tanto por la infección con SARS-CoV-2, como por distintos esquemas y protocolos de vacunación en diferentes poblaciones de individuos. Asimismo, permite evaluar la respuesta inmunológica T generada frente a nuevas variantes del virus e identificar individuos sanos resistentes a SARS-CoV-2 con inmunidad pre-existente hacia coronavirus estacionales.

Abstract The rapid spread of the SARS-CoV-2, the caus ative agent of the emergent pandemic disease COVID-19, requires the urgent commitment of the immunology community to understand the adaptive immune response developed by COVID-19 convalescent patients and individuals vaccinated with different strategies and schemes, with the ultimate goal of implementing and optimizing health care and prevention policies. Currently, assessment of SARS-CoV-2-specific immunity is mainly focused on the measurement of the antibody titers and analysis of their neutralizing capacity. However, a considerable proportion of individuals lack humoral responses or show a progressive decline of SARS-CoV-2-specific neutral izing antibodies. In order to study the cellular response of convalescent patients and vaccinated individuals, we have developed the 'COVID-T Platform', an optimized strategy to study SARS-CoV-2-specific T cell responses. This platform allows assessment of the nature, magnitude and persistence of antigen-specific T-cell immunity in COVID-19-convalescent patients and vaccinated individuals. Moreover, it gives the opportunity to study cellular responses against emerging coronavirus variants and to identify individuals with cross-reactive immunity against seasonal coronaviruses.

Inmunoterapia pasiva con anticuerpos policlonales equinos (suero equino hiperinmune) para el tratamiento de pacientes con COVID-19 / Passive immunotherapy with equine polyclonal antibodies (hyperimmune equine serum) for the treatment of patients with COVID-19

INTRODUCIÓN: El presente informe es producto del trabajo colaborativo de la Comisión Nacional de Evaluación de Tecnologías de Salud (CONETEC), dependiente del Ministerio de Salud de la Nación y creada por RM N° 623/2018. La CONETEC realiza evaluaciones y emite recomendaciones a la autoridad sanitaria sobre la incorporación, forma de uso, financiamiento y políticas de cobertura de las tecnologías sanitarias desde una perspectiva global del sistema de salud argentino. En sus evaluaciones y recomendaciones, la CONETEC tiene en cuenta criterios de calidad, seguridad, efectividad, eficiencia y equidad, evaluados bajo dimensiones éticas, médicas, económicas y sociales. Sus resultados son consensuados mediante discusiones públicas y ponderados a través de un marco de valor explícito, con la participación de todos los actores involucrados en el proceso de toma de decisiones en salud. Los informes y recomendaciones de esta comisión surgen de este proceso público, transparente y colaborativo, siendo de libre consulta y acceso para toda la sociedad. El objetivo del presente informe es evaluar parámetros de eficacia, seguridad y conveniencia de anticuerpos policlonales equinos (suero equino hiperinmune) para el tratamiento de pacientes con COVID-19. OBJETIVO El objetivo del presente informe es evaluar parámetros de eficacia, seguridad y conveniencia de anticuerpos policlonales equinos (suero equino hiperinmune) para el tratamiento de pacientes con COVID-19. METODOLOGÍA: Realizamos una evaluación "viva" (con un proceso de actualización continua) de una tecnología sanitaria, basada en evidencia proveniente de revisiones sistemáticas "vivas" de referencia y guías de práctica clínica de alta calidad metodológica para brindar parámetros actualizados y balanceados que sean de utilidad para la toma de decisiones en los diferentes niveles de gestión. RESULTADOS: Se identificó una revisión sistemática que cumple con los criterios de inclusión del presente informe. Adicionalmente se identificaron otras dos revisiones sistemáticas con adecuado proceso de desarrollo pero ninguna contestó la pregunta pertinente al presente informe. La revisión sistemática identificada incluyó un estudio aleatorizado con un total de 243 pacientes aleatorizados a suero equino hiperinmune o placebo. Se realizaron múltiples análisis de subgrupo incluyendo uno que comparó pacientes según su severidad al comienzo del estudio. Ninguno de estos análisis mostró resultados que sugieran un efecto diferencial en los subgrupos comparados. CONCLUSIONES: El cuerpo de evidencia disponible hasta el momento muestra que existe incertidumbre en el efecto de los anticuerpos policlonales equinos (suero equino hiperinmune) sobre la mortalidad y el ingreso en ventilación mecánica. El uso de anticuerpos policlonales equinos (suero equino hiperinmune) podría impactar positivamente en el tiempo de mejoría clínica, pero podría no incrementar la proporción de pacientes que alcanzan la recuperación clínica que lleva al alta hospitalaria. Los anticuerpos policlonales equinos (suero equino hiperinmune) podrían no asociarse a afectos adversos severos. La incertidumbre sobre el efecto de la tecnología evaluada sobre los desenlaces críticos para pacientes hospitalizados con COVI-19 (mortalidad y requerimiento de ventilación invasiva) determina que la certeza en los efectos de suero equino sobre la salud de pacientes con COVID-19 sea muy baja. A pesar que la tecnología se produce en Argentina lo que facilitaría su acceso, encontramos barreras relacionadas con una amplia población objetivo y elevado costo comparativo de esta intervención que podrían acarrear problemas de producción y afectar la distribución equitativa en situaciones de alta demanda. No identificamos recomendaciones con el rigor metodológico apropiado para ser incluidas en el informe.