Salivary assessment of the immune/inflammatory responses and oxidative stress in older adults vaccinated with CoronaVac or ChadOx-1.

BACKGROUND: Although important information concerning COVID-19 vaccination is available, the effects of the CoronaVac and ChadOx-1 vaccines on immunity and the redox balance in the upper airway mucosa of the aged population are not fully understood. Therefore, the aim of this study was to investigate the impacts of two doses of the CoronaVac or ChadOx-1 vaccine on immune/inflammatory responses and oxidative stress in the airway mucosa of older adults. METHODS: Seventy-six older adults of both sexes, with a mean age of 75.1 ± 6.4 years, were separated according to vaccination status into the CoronaVac (n = 52) and ChadOx-1 (n = 24) groups. Saliva samples were collected before (pre) and 30 days after (post) the administration of the second dose of the CoronaVac or ChadOx-1 vaccine to assess the levels of antibodies (sIgA and IgG), antimicrobial peptides, cytokines, and oxidant/antioxidant agents. RESULTS: The immunogenicity in the ChadOx-1 group was 37.5% for sIgA and 25% for IgG, while that in the CoronaVac group was 18.9% for sIgA and 13.2% for IgG. Intergroup analysis revealed that (1) lower levels of IFN-α, IFN-γ, and IL-10 and a greater IFN-γ/IL-10 ratio, in addition to a greater IL-6/IL-10 ratio, were found in both the pre- and postvaccination periods, and (2) lower levels of total sIgA, IL-12p70, IL-17A, TNF-α, and the IL-12p70/IL-10 ratio, in addition to higher levels of specific sIgA for SARS-CoV-2 antigens and lysozyme, were observed only in the postvaccination period in the ChadOx-1 group than in the CoronaVac group. Intragroup analysis revealed (1) a significant increase in the salivary levels of total peroxides in the postvaccination period compared to those in the prevaccination period in both volunteer groups; (2) a decrease in the levels of lysozyme and the ratio between total antioxidant capacity (TAC) and total peroxides in the postvaccination period in the CoronaVac group compared with those in the prevaccination period; and (3) decreases in the TNF-α, IL-6, and IL-12p70 levels, and the IL-12p70/IL-10 ratio in the ChadoX-1 group, as well as a higher lactoferrin concentration in the postvaccination period than in the prevaccination period. Several positive and negative correlations between the parameters assessed here were found. CONCLUSIONS: In general, the ChadOx-1 group exhibited improvements in both immune/inflammatory responses and redox balance and greater immunogenicity than did the CoronaVac group.

Combination of Live and Inactivated Salmonella Vaccines to Protect Against Fowl Typhoid in Laying Hens.

Fowl typhoid (FT) caused by Salmonella Gallinarum (SG) is a poultry disease distributed worldwide that has been eradicated in commercial production of many developed countries but still persists in many developing countries. Vaccination is one of the main strategies to reduce mortality, clinical signs, and vertical or horizontal transmission. The aim of this work was to assess the protection against FT conferred by vaccines based on Salmonella Enteritidis (SE), SG, or a combination. Five experimental groups of birds, vaccinated with different live or inactivated SG and SE vaccines were included in the trial: 1) two doses of a SG-SE bivalent inactivated vaccine; 2) four doses of the live attenuated SE vaccine; 3) three doses of the live attenuated SE vaccine and two doses of the SG-SE bivalent inactivated vaccine; 4) two doses of the live attenuated SG9R vaccine; and 5) unvaccinated birds. At 28 wk of age, all hens were challenged with a virulent strain of SG, and mortality was recorded during the subsequent 15 days. The results showed that the plan that included only the inactivated vaccine did not show significant protection (P = 1), while the plan based on the administration of the attenuated strain of SE significantly reduced mortality in the group of birds (P = 0.0309). However, the highest levels of protection were obtained in the group of hens immunized with the combination of the inactivated vaccine and the live attenuated SE strain (P < 0.0001), which was statistically similar to the homologous protection conferred by the SG 9R strain, a vaccine used in many countries to control FT. These results demonstrate that the combination of existing vaccines together with strict biosecurity measures on farms may help improve the control of the pathogen in countries where FT in an emerging or reemerging disease.

Nota de investigación- Combinación de vacunas vivas e inactivadas contra Salmonella para proteger contra la tifoidea aviar en gallinas de postura. La tifoidea aviar (FT) causada por Salmonella enterica serotipo Gallinarum biovar Gallinarum (SG) es una enfermedad distribuida en todo el mundo que ha sido erradicada de la producción av'icola comercial de muchos pa'ises desarrollados pero que aún persiste en muchos pa'ises en desarrollo. La vacunación es una de las principales estrategias para reducir la mortalidad, los signos cl'inicos y la transmisión vertical u horizontal. El objetivo de este trabajo fue evaluar la protección contra la tifoidea aviar conferida por vacunas elaboradas con Salmonella enterica serotipo Enteritidis (SE), SG o una combinación de ellas. Se incluyeron en el ensayo cinco grupos experimentales de aves, vacunadas con diferentes vacunas de SG y SE vivas o inactivadas: 1) dos dosis de una vacuna bivalente inactivada de SG y SE; 2) cuatro dosis de la vacuna SE viva atenuada; 3) tres dosis de vacuna SE viva atenuada y dos dosis de vacuna bivalente inactivada SG y SE; 4) dos dosis de la vacuna SG 9R viva atenuada; y 5) aves no vacunadas. A las 28 semanas de edad, todas las gallinas fueron expuestas a una cepa virulenta de SG y se registró la mortalidad durante los 15 d'ias siguientes. Los resultados mostraron que el plan que inclu'ia solo la vacuna inactivada no mostró protección significativa (P=1), mientras que el plan basado en la administración de la cepa atenuada de S. Enteritidis redujo significativamente la mortalidad en el grupo de aves (P = 0,0309). Sin embargo, los mayores niveles de protección se obtuvieron en el grupo de gallinas inmunizadas con la combinación de la vacuna inactivada y la cepa viva atenuada de SE (P < 0,0001), la cual fue estad'isticamente similar a la protección homóloga conferida por la cepa de SG 9R, que es una vacuna utilizada en muchos pa'ises para controlar la tifoidea aviar. Estos resultados demuestran que la combinación de las vacunas existentes junto con estrictas medidas de bioseguridad en las granjas puede ayudar a mejorar el control del patógeno en pa'ises donde la tifoidea aviar es una enfermedad emergente o reemergente.

Influence of previous COVID-19 exposure and vaccine type (CoronaVac, ChAdOx1 nCov-19 or BNT162b2) on antibody and cytokine (Th1 or Th2) responses.

To achieve global herd immunity, widespread vaccination is the most effective strategy. Vaccines stimulate the immune system, generating cytokines and chemokines, isotype antibodies, and neutralizing antibodies; all these molecules collectively provide a more comprehensive characterization of the immune response post-vaccination. We conducted a longitudinal study in northwestern Mexico, involving 120 individuals before vaccination and after the first dose of the SARS-CoV-2 vaccine, and 46 individuals after their second dose. Our findings reveal that antibody levels stabilize over time; cytokine levels generally increase following the first dose but decrease after the second dose and higher than normal levels in IgG1 and IgG3 concentrations are present. Most of the innate cytokines determined in this study were higher after the first dose of the vaccine. Regardless of previous infection history, this finding suggests that the first dose of the vaccine is crucial and may stimulate immunity by enhancing the innate immune response. Conversely, increased levels of IL-4, indicative of a Th2 response, were found in individuals without prior exposure to the virus and in those vaccinated with CoronaVac. These results suggest that the immune response to COVID-19 vaccines is multi-faceted, with preexisting immunity potentiating a more robust innate response. Vaccine type plays a critical role, with genetic vaccines favoring a Th1 response and inactivated vaccines like CoronaVac skewing toward a Th2 profile.

Assessment of immune responses to a Comirnaty® booster following CoronaVac® vaccination in healthcare workers.

BACKGROUND: The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. OBJECTIVES: To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. METHODS: Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. FINDINGS: Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. MAIN CONCLUSIONS: The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.

Effectiveness of CoronaVac in the prevention of COVID-19, a test-negative case-control study in Brazil.

The present study aimed to evaluate the effectiveness of two doses of CoronaVac in preventing SARS-CoV-2 symptomatic disease with virological confirmation, as well as in the prevention of COVID-19 moderate and severe cases. A test-negative unmatched case-control design was used, in which cases were patients with suspected COVID-19 (presenting at least two of the following symptoms: fever, chills, sore throat, headache, cough, runny nose, olfactory or taste disorders) with virological confirmation, and controls were those whose SARS-CoV-2 test was negative. As for exposure, participants were classified as unvaccinated, or vaccinated with a complete schedule. Suspected COVID-19 cases were identified from March to November 2021, in two cities located in the State of São Paulo, Brazil. All participants signed the Informed Consent Form before enrollment. RT-PCR results and vaccination data were obtained from the local surveillance systems. Up to two phone calls were made to obtain information on the outcome of the cases. A total of 2981 potential participants were screened for eligibility, of which 2163 were included, being 493 cases and 1670 controls. Vaccination, age, the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset, and the educational level were the variables independently associated with the outcome. The adjusted vaccine effectiveness for symptomatic COVID-19 (AVE) was 39.0 % (95 % CI 6.0-60.0 %). The AVE in the prevention of moderate and severe disease was 91.0 % (95 % CI 76.0-97.0 %). Our results were influenced by the waning of the Gamma variant, in the second trimester of 2021, followed by the increase in vaccination coverage, and a drop in the number of cases in the second half of the year. The study demonstrated the high effectiveness of CoronaVac in preventing moderate/severe COVID-19 cases.

Shedding reduction and immunity modulation in piglets with an inactivated Mycoplasma hyopneumoniae vaccine encapsulated in nanostructured SBA-15 silica.

Mycoplasma (M.) hyopneumoniae is a primary etiological agent of porcine enzootic pneumonia (PEP), a disease that causes significant economic losses to pig farming worldwide. Current commercial M. hyopneumoniae vaccines induce partial protection, decline in preventing transmission of this pathogen or inducing complete immunity, evidencing the need for improving vaccines against PEP. In our study, we aimed to test the effectiveness of the SBA-15 ordered mesoporous silica nanostructured particles as an immune adjuvant of a vaccine composed of M. hyopneumoniae strain 232 proteins encapsulated in SBA-15 and administered by intramuscular route in piglets to evaluate the immune responses and immune-protection against challenge. Forty-eight 24-day-old M. hyopneumoniae-free piglets were divided into four experimental groups with different protocols, encompassing a commercial vaccine against M. hyopneumoniae, SBA-15 vaccine, SBA-15 adjuvant without antigens and a non-immunized group. All piglets were challenged with the virulent strain 232 of M. hyopneumoniae. Piglets that received the SBA-15 and commercial vaccine presented marked immune responses characterized by anti-M. hyopneumoniae IgA and IgG antibodies in serum, anti-M. hyopneumoniae IgA antibodies in nasal mucosa and showed an upregulation of IL-17 and IL-4 cytokines and downregulation of IFN-γ in lungs 35 days post-infection. Piglets immunized with SBA-15 vaccine presented a reduction of bacterial shedding compared to piglets immunized with a commercial bacterin. In addition, piglets from SBA-15 adjuvant suspension group presented increased IL-17 gene expression in the lungs without involvement of Th1 and Th2 responses after challenge. These results indicated that SBA-15 vaccine induced both humoral and cell-mediated responses in the upper respiratory tract and lungs, first site of replication and provided protection against M. hyopneumoniae infection with a homologous strain with reduction of lung lesions and bacterial shedding. Finally, these results enhance the potential use of new technologies such as nanostructured particles applied in vaccines for the pig farming industry.

Real-world effectiveness of the CoronaVac vaccine in a retrospective population-based cohort in four Colombian cities (2021-2022).

OBJECTIVES: The National Vaccination Plan against SARS-CoV-2/COVID-19 was launched by the Ministry of Health and Social Protection on 14 February 2021. The main objective of this study was to evaluate the effectiveness of the CoronaVac in preventing the three clinical outcomes of infection, hospitalisation, or death, in a real-world scenario. DESIGN: This was a population-based retrospective dynamic cohort study using a multivariate Cox model to calculate hazard ratios to estimate vaccine effectiveness from 17 February 2021 to 30 June 2022. The data were collected from surveillance systems for 12 months for each individual. Four cities were selected on the basis of the reliability of their data bases. RESULTS: The rates of CoronaVac effectiveness were 32% (95% confidence interval [CI] 31-33) for preventing infection, 55% (95% CI 54-56) for hospitalisation, and 90% (95% CI 89-90) for death, at the end of follow-up. These findings were more consistent during the first 4 months. Compared with the unvaccinated group, homologous booster doses appeared to increase effectiveness in preventing hospitalisation, whereas heterologous booster doses increased protection for both hospitalisation and death. Booster doses did not improve effectiveness among those already vaccinated with CoronaVac, even when they received heterologous boosters. CONCLUSIONS: CoronaVac demonstrated effectiveness in preventing death and hospitalisation during the first year of follow-up, but its effectiveness in preventing infection was lower, decreasing rapidly after the first 4 months of follow-up. The effectiveness was higher among children aged between 3 and 12 years, and among adults aged ≥60 years. Booster doses did not improve effectiveness among those already vaccinated with CoronaVac.

Safety of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with rheumatoid arthritis: data from the Brazilian multicentric study safer.

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA. OBJECTIVE: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA. METHODS: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose. RESULTS: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines. CONCLUSION: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.

Efficacy, immunogenicity and safety of CoronaVac® in children and adolescents aged 6 months to 17 years: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.

Safe and effective vaccines against COVID-19 for children and adolescents are needed. This international multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial assessed the efficacy, immunogenicity, and safety of CoronaVac® in children and adolescents (NCT04992260). The study was carried out in Chile, South Africa, Malaysia, and the Philippines. The enrollment ran from September 10, 2021 to March 25, 2022. For efficacy assessment, the median follow-up duration from 14 days after the second dose was 169 days. A total of 11,349 subjects were enrolled. Two 3-µg injections of CoronaVac® or placebo were given 28 days apart. The primary endpoint was the efficacy of the CoronaVac®. The secondary endpoints were the immunogenicity and safety. The vaccine efficacy was 21.02% (95% CI: 1.65, 36.67). The level of neutralizing antibody in the vaccine group was significantly higher than that in the placebo group (GMT: 390.80 vs. 62.20, P <0.0001). Most adverse reactions were mild or moderate. All the severe adverse events were determined to be unrelated to the investigational products. In conclusion, in the Omicron-dominate period, a two-dose schedule of 3 µg CoronaVac® was found to be safe and immunogenic, and showed potential against symptomatic COVID-19 in healthy children and adolescents.

Antibody persistence 7 years after hepatitis-A vaccine in children with human immunodeficiency virus infection.

BACKGROUND: HIV-infected children have a higher risk of presenting infections, including the hepatitis A virus (HAV). The inactivated HAV vaccine is immunogenic in immunocompetent hosts; however, there are insufficient studies on the duration of seroprotection in HIV-infected children. METHODS: An analytical cohort study was conducted. HIV-1-infected children who received the inactivated HAV vaccine (2 doses) were included. Blood samples were taken for antibody measurement, the first one 28 days after the second dose and another 7 years after the vaccination schedule. Information on viral load, immunological category, weight, height, and response to antiretroviral treatment from diagnosis to the last assessment was obtained. RESULTS: 19 patients were included, with a mean age of 12.6 years (SD ± 2.29). 58% were male. 80% of the patients presented protective immunoglobulin G antibodies against HAV 7-year post-vaccination. The antibody concentration was found to be between 13 and 80 mIU/mL (median of 80 mIU/mL). 52% showed some degree of immunosuppression. There was no statistically significant relationship between the presence of seroprotection and viral load, treatment failure, immunological category, and malnutrition. Twelve patients presented with antiretroviral treatment failure, and in 33% of them, the antibodies did not offer satisfactory seroprotection. CONCLUSION: 7-year post-vaccination, 80% of HIV-infected children maintain seroprotection titers against HAV.

INTRODUCCIÓN: Los niños infectados por el virus de la inmunodeficiencia humana (VIH) tienen mayor riesgo de presentar infecciones, incluyendo hepatitis por virus A (VHA). La vacuna inactivada contra el VHA es inmunógena en el huésped inmunocompetente. No hay estudios suficientes sobre el tiempo de seroprotección en niños infectados por el VIH. MÉTODO: Estudio de cohorte, analítico. Se incluyeron niños con infección por VIH-1 que recibieron la vacuna inactivada contra el VHA (dos dosis). Se les tomaron muestras sanguíneas para medición de anticuerpos, una 28 días después de la segunda dosis y otra 7 años después del esquema de vacunación. Se obtuvo información de carga viral, categoría inmunológica, peso y talla, y respuesta al tratamiento antirretroviral desde el diagnóstico hasta la última valoración. RESULTADOS: Se incluyeron 19 pacientes con una edad media de 12.6 años (± 2.29). El 58% fueron del sexo masculino. El 80% de los pacientes presentaron anticuerpos immunoglobulin G (IgG) contra el VHA protectores a los 7 años de la vacunación. La concentración de anticuerpos se encontró entre 13 y 80 mUI/ml (mediana: 80 mUI/ml). El 52% mostraron algún grado de inmunosupresión. No existe relación estadísticamente significativa entre la presencia de seroprotección y la carga viral, la falla al tratamiento, la categoría inmunológica ni la desnutrición. Doce pacientes presentaron falla al tratamiento antirretroviral; en el 33% de ellos los anticuerpos no ofrecían seroprotección satisfactoria. CONCLUSIONES: A 7 años posvacunación, el 80% de los niños con VIH mantienen títulos de seroprotección frente al VHA.

Second booster dose improves antibody neutralization against BA.1, BA.5 and BQ.1.1 in individuals previously immunized with CoronaVac plus BNT162B2 booster protocol.

Introduction: SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses. Methods: To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate. Results: The findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m). Discussion: Our study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons.

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

How has research on the effectiveness and safety of COVID-19 vaccination been evaluated: a scope review with emphasis on CoronaVac.

Introduction: The control of the COVID-19 epidemic has been focused on the development of vaccines against SARS-CoV-2. All developed vaccines have reported safety and efficacy results in preventing infection and its consequences, although the quality of evidence varies depending on the vaccine considered. Different methodological designs have been used for their evaluation, which can influence our understanding of the effects of these interventions. CoronaVac is an inactivated vaccine, and it has been assessed in various studies, including clinical trials and observational studies. Given these differences, our objective was to explore the published information to answer the question: how has the efficacy/effectiveness and safety of CoronaVac been evaluated in different studies? This is to identify potential gaps and challenges to be addressed in understanding its effect. Methods: A scoping review was carried out following the methodology proposed by the Joanna Briggs Institute, which included studies carried out in humans as of 2020, corresponding to systematic reviews, clinical trials, analytical or descriptive observational studies, in which the effectiveness and/or safety of vaccines for COVID19 were evaluated or described. There were no age restrictions for the study participants. Results: The efficacy/effectiveness and safety of this vaccine was assessed through 113 studies. Nineteen corresponded to experimental studies, 7 of Phase II, 5 of Phase IV, and 4 were clinical trials with random assignment. Although some clinical trials with random assignment have been carried out, these have limitations in terms of feasibility, follow-up times, and with this, the possibility of evaluating safety outcomes that occur with low frequencies. Not all studies have used homogeneous methods of analysis. Both the prevention of infection, and the prevention of outcomes such as hospitalization or death, have been valued through similar outcomes, but some through multivariate analysis of dependencies, and others through analysis that try to infer causally through different control methods of confounding. Conclusion: Published information on the evaluation of the efficacy/effectiveness and safety of the CoronaVac is abundant. However, there are differences in terms of vaccine application schedules, population definition, outcomes evaluated, follow-up times, and safety assessment, as well as non-standardization in the reporting of results, which may hinder the generalizability of the findings. It is important to generate meetings and consensus strategies for the methods and reporting of this type of studies, which will allow to reduce the heterogeneity in their presentation and a better understanding of the effect of these vaccines.

Recent progress and major gaps in the vaccine development for African swine fever.

The swine industry across the globe is recently facing a devastating situation imparted by a highly contagious and deadly viral disease, African swine fever. The disease is caused by a DNA virus, the African swine fever virus (ASFV) of the genus Asfivirus. ASFV affects both wild boars and domestic pigs resulting in an acute form of hemorrhagic fever. Since the first report in 1921, the disease remains endemic in some of the African countries. However, the recent occurrence of ASF outbreaks in Asia led to a fresh and formidable challenge to the global swine production industry. Culling of the infected animals along with the implementation of strict sanitary measures remains the only options to control this devastating disease. Efforts to develop an effective and safe vaccine against ASF began as early as in the mid-1960s. Different approaches have been employed for the development of effective ASF vaccines including inactivated vaccines, subunit vaccines, DNA vaccines, virus-vectored vaccines, and live attenuated vaccines (LAVs). Inactivated vaccines are a non-feasible strategy against ASF due to their inability to generate a complete cellular immune response. However genetically engineered vaccines, such as subunit vaccines, DNA vaccines, and virus vector vaccines, represent tailored approaches with minimal adverse effects and enhanced safety profiles. As per the available data, gene deleted LAVs appear to be the most potential vaccine candidates. Currently, a gene deleted LAV (ASFV-G-∆I177L), developed in Vietnam, stands as the sole commercially available vaccine against ASF. The major barrier to the goal of developing an effective vaccine is the critical gaps in the knowledge of ASFV biology and the immune response induced by ASFV infection. The precise contribution of various hosts, vectors, and environmental factors in the virus transmission must also be investigated in depth to unravel the disease epidemiology. In this review, we mainly focus on the recent progress in vaccine development against ASF and the major gaps associated with it.

Monitoring of antibody levels in healthcare workers after inactivated coronavirus disease 19 vaccination.

OBJECTIVE: Because of the coronavirus disease 19 pandemic, studies on vaccination are being conducted in our country as well as across the world. In this study, the antibody levels in healthcare workers vaccinated with two doses of inactivated vaccine and the factors affecting these levels were investigated. METHODS: Randomly selected volunteers from healthcare workers, who had been vaccinated with two doses of inactivated vaccine in January to February 2021, were included in the study. Blood samples were drawn twice, 1 month and 6 months after the second dose vaccine (CoronaVac:Sinovac Life Science Co, Ltd, Beijing, China). The antibody levels were determined by the chemiluminescence microparticle immunoassay method using kits for quantitative detection of immunoglobulin class G antibodies to severe acute respiratory syndrome coronavirus 2. RESULTS: The mean antibody levels of 129 volunteers were 1232.5 (min: 103 to max: 7151) AU/mL in the first month and 403.5 (min: 23 to max: 4963) AU/mL in the sixth month. According to the survey results, 91 (71%) volunteers had not been diagnosed with coronavirus disease 19 before vaccination. The antibody levels 1 month and 6 months after the second dose of vaccination were significantly higher in those who had been diagnosed with coronavirus disease 19 before vaccination than in those who had not. It was found that age, gender, fast food, or healthy nutrition had no effect on antibody levels. CONCLUSION: Vaccines are very important both to protect against coronavirus disease 19 and to experience only a mild form of the disease. Immunoglobulin class G levels formed after vaccination may be affected by many factors and may decrease over time.

Development, Histological, and Ultrastructural Evaluation of Sheep Hyperimmune Serum Therapy for COVID-19 / Desarrollo, Evaluación Histológica y Ultraestructural de la Terapia con Suero Hiperinmune de Oveja para COVID-19

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN).

BACKGROUND: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. METHODS: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). RESULTS: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. CONCLUSIONS: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

COVID-19 inactivated and non-replicating viral vector vaccines induce regulatory training phenotype in human monocytes under epigenetic control.

Background: Trained immunity is the enhanced innate immune response resulting from exposure to pathogens or vaccines against an unrelated pathogen stimulus. Certain vaccines induce a memory like response in monocytes and NK cells, leading to modulation in cytokine production, metabolic changes, and modifications in histone patterns. Here, we hypothesized that vaccination against SARS-CoV-2 could induce the training of monocytes in addition to stimulating the adaptive immune response. Methods: Therefore, we aimed to investigate the immunophenotyping, cytokine and metabolic profile of monocytes from individuals who were completely immunized with two doses of inactivated COVID-19 vaccine or non-replicating viral vector vaccine. Subsequently, we investigated the epigenetic mechanisms underlying monocyte immune training. As a model of inflammatorychallenge, to understand if the monocytes were trained by vaccination and how they were trained, cells were stimulated in vitro with the endotoxin LPS, an unrelated stimulus that would provoke the effects of training. Results: When challenged in vitro, monocytes from vaccinated individuals produced less TNF-α and those who received inactivated vaccine produced less IL-6, whereas vaccination with non-replicating viral vector vaccine induced more IL-10. Inactivated vaccine increased classical monocyte frequency, and both groups showed higher CD163 expression, a hallmark of trained immunity. We observed increased expression of genes involved in glycolysis and reduced IRG1 expression in vaccinated subjects, a gene associated with the tolerance phenotype in monocytes. We observed that both vaccines reduced the chromatin accessibility of genes associated with the inflammatory response, the inactivated COVID-19 vaccine trained monocytes to a regulatory phenotype mediated by histone modifications in the IL6 and IL10 genes, while the non-replicating viral vector COVID-19 vaccine trained monocytes to a regulatory phenotype, mediated by histone modifications in the IL6, IL10, TNF, and CCL2 genes. Conclusions: Our findings support the recognized importance of adopting vaccination against SARS CoV-2, which has been shown to be effective in enhancing the adaptive immune response against the virus and reducing mortality and morbidity rates. Here, we provide evidence that vaccination also modulates the innate immune response by controlling the detrimental inflammatory response to unrelated pathogen stimulation.

A roadmap for developing Venezuelan equine encephalitis virus (VEEV) vaccines: Lessons from the past, strategies for the future.

Venezuelan equine encephalitis (VEE) is a zoonotic infectious disease caused by the Venezuelan equine encephalitis virus (VEEV), which can lead to severe central nervous system infections in both humans and animals. At present, the medical community does not possess a viable means of addressing VEE, rendering the prevention of the virus a matter of paramount importance. Regarding the prevention and control of VEEV, the implementation of a vaccination program has been recognized as the most efficient strategy. Nevertheless, there are currently no licensed vaccines or drugs available for human use against VEEV. This imperative has led to a surge of interest in vaccine research, with VEEV being a prime focus for researchers in the field. In this paper, we initially present a comprehensive overview of the current taxonomic classification of VEEV and the cellular infection mechanism of the virus. Subsequently, we provide a detailed introduction of the prominent VEEV vaccine types presently available, including inactivated vaccines, live attenuated vaccines, nucleic acid, and virus-like particle vaccines. Moreover, we emphasize the challenges that current VEEV vaccine development faces and suggest urgent measures that must be taken to overcome these obstacles. Notably, based on our latest research, we propose the feasibility of incorporation codon usage bias strategies to create the novel VEEV vaccine. Finally, we prose several areas that future VEEV vaccine development should focus on. Our objective is to encourage collaboration between the medical and veterinary communities, expedite the translation of existing vaccines from laboratory to clinical applications, while also preparing for future outbreaks of new VEEV variants.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults.

BACKGROUND: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. METHODS: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. FINDINGS: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. INTERPRETATION: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. FUNDING: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.