Epitranscriptomic regulation of HIV-1 full-length RNA packaging.

During retroviral replication, the full-length RNA serves both as mRNA and genomic RNA. However, the mechanisms by which the HIV-1 Gag protein selects the two RNA molecules that will be packaged into nascent virions remain poorly understood. Here, we demonstrate that deposition of N6-methyladenosine (m6A) regulates full-length RNA packaging. While m6A deposition by METTL3/METTL14 onto the full-length RNA was associated with increased Gag synthesis and reduced packaging, FTO-mediated demethylation promoted the incorporation of the full-length RNA into viral particles. Interestingly, HIV-1 Gag associates with the RNA demethylase FTO in the nucleus and contributes to full-length RNA demethylation. We further identified two highly conserved adenosines within the 5'-UTR that have a crucial functional role in m6A methylation and packaging of the full-length RNA. Together, our data propose a novel epitranscriptomic mechanism allowing the selection of the HIV-1 full-length RNA molecules that will be used as viral genomes.

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of ß-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Sustainable and circular agro-environmental practices: A review of the management of agricultural waste biomass in Spain and the Czech Republic.

Sustainable and circular production models, such as the circular economy and circular bioeconomy, have become key mechanisms to leave behind the traditional linear model of food production. Under this approach and considering the waste biomass potential available in Spain and the Czech Republic, the main objective of this study is to analyse the most relevant aspects of the generation, use and regulation of agricultural waste biomass (AWB) in both countries. For this purpose, a scientometric analysis and systematic review of published research in the Scopus database were carried out. A complementary analysis of AWB management policies and regulations was also part of the methodology. The results show that Spain has published almost twice as much research as the Czech Republic. Furthermore, 91% of the retrieved research prioritizes the characterization and estimation of the potential of more than 15 AWB types. Among the main ones are olive residues, horticultural residues and wheat straw, which are used for producing organic amendments, bioenergy and biofuels. The results confirm that the reduction and valorization of AWB is an issue that has become more important in the last 13 years, mainly due to the policies and strategies for circular economy and circular bioeconomy. With this in mind, this study provides relevant information for governments on the aspects that need to be improved to advance in the valorization of AWB. This study also provides guidance to farmers on the reduction and/or recovery alternatives that they can implement to move towards sustainable and circular agriculture.

The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030.

Cardiovascular disease is the leading cause of death in women. Decades of grassroots campaigns have helped to raise awareness about the impact of cardiovascular disease in women, and positive changes affecting women and their health have gained momentum. Despite these efforts, there has been stagnation in the overall reduction of cardiovascular disease burden for women in the past decade. Cardiovascular disease in women remains understudied, under-recognised, underdiagnosed, and undertreated. This Commission summarises existing evidence and identifies knowledge gaps in research, prevention, treatment, and access to care for women. Recommendations from an international team of experts and leaders in the field have been generated with a clear focus to reduce the global burden of cardiovascular disease in women by 2030. This Commission represents the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.

Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 spike antibodies.

BACKGROUND: Chile was severely affected by COVID19 outbreaks but was also one of the first countries to start a nationwide program to vaccinate against the disease. Furthermore, Chile became one of the fastest countries to inoculate a high percentage of the target population and implemented homologous and heterologous booster schemes in late 2021 to prevent potential immunological waning. The aim of this study is to compare the immunogenicity and time course of the humoral response elicited by the CoronaVac vaccine in combination with homologous versus heterologous boosters. METHODS: We compared the immunogenicity of two doses of CoronaVac and BNT162b2 vaccines and one homologous or heterologous booster through an ELISA assay directed against the ancestral spike protein of SARS-CoV-2. Sera were collected from individuals during the vaccination schedule and throughout the implementation of homologous and heterologous booster programs in Chile. RESULTS: Our findings demonstrate that a two-dose vaccination scheme with CoronaVac induces lower levels of anti-SARS-CoV-2 spike antibodies than BNT162b2 in a broad age range (median age 42 years; interquartile range (IQR) 27-61). Furthermore, antibody production declines with time in individuals vaccinated with CoronaVac and less noticeably, with BNT162b2. Analysis of booster schemes revealed that individuals vaccinated with two doses of CoronaVac generate immunological memory against the SARS-CoV-2 ancestral strain, which can be re-activated with homologous or heterologous (BNT162b2 and ChAdOx1) boosters. Nevertheless, the magnitude of the antibody response with the heterologous booster regime was considerably higher (induction fold BNT162b2: 11.2x; ChAdoX1; 12.4x; CoronaVac: 6.0x) than the responses induced by the homologous scheme. Both homologous and heterologous boosters induced persistent humoral responses (median 122 days, IQR (108-133)), although heterologous boosters remained superior in activating a humoral response after 100 days. CONCLUSIONS: Two doses of CoronaVac induces antibody titers against the SARS-CoV-2 ancestral strain which are lower in magnitude than those induced by the BNT162b2 vaccine. However, the response induced by CoronaVac can be greatly potentiated with a heterologous booster scheme with BNT162b2 or ChAdOx1 vaccines. Furthermore, the heterologous and homologous booster regimes induce a durable antibody response which does not show signs of decay 3 months after the booster dose.

Sustainability and circularity in fruit and vegetable production. Perceptions and practices of reduction and valorization of agricultural waste biomass in south-eastern Spain.

This study aims to conduct an exploratory and comparative analysis between Fruit and Vegetable Producer Organizations (FVPOs) and fruit and vegetable producers that are not part of these organizations (Non-FVPOs) regarding the prioritization, perception, and adoption of sustainable and circular practices. For this purpose, data was collected from both groups through an online survey. Statistical techniques for the comparison of two independent groups (chi-square test, Fisher's exact test, and Mann-Whitney U test) were used to examine the differences on a sample of 14 FVPOs and 22 Non-FVPOs from Spain. Although the results show more similarities than differences between the two groups, they highlight that FVPOs are more likely to prioritize environmental factors and implement both green manuring and biodegradable raffia as the main Agricultural Waste Biomass (AWB) reduction and/or valorization practices. In addition, the findings point to the relevance of environmental considerations and specifically to the Sustainable and Circular Production Models (SCPMs) as an alternative to the traditional fruit and vegetable production system. Theoretically, the results mainly contradict resource and first mover advantage arguments by revealing that more resourceful organizations do not necessarily possess better environmental management. This study also provides innovative information and relevant contributions for governments. It allows them to identify aspects that should be strengthened in relation to policies, regulatory frameworks, and/or strategies that promote sustainable and circular production systems for both FVPOs and Non-FVPOs. In addition, it contributes with implications, for organizations and farmers, how to improve actions and opportunities to advance the transition to SCPMs.

CBP80/20-dependent translation initiation factor (CTIF) inhibits HIV-1 Gag synthesis by targeting the function of the viral protein Rev.

Translation initiation of the human immunodeficiency virus type-1 (HIV-1) full-length RNA has been shown to occur through cap-dependent and IRES-driven mechanisms. Previous studies suggested that the nuclear cap-binding complex (CBC) rather than eIF4E drives cap-dependent translation of the full-length RNA and we have recently reported that the CBC subunit CBP80 supports the function of the viral protein Rev during nuclear export and translation of this viral transcript. Ribosome recruitment during CBC-dependent translation of cellular mRNAs relies on the activity CBP80/20 translation initiation factor (CTIF), which bridges CBP80 and the 40S ribosomal subunit through interactions with eIF3g. Here, we report that CTIF inhibits HIV-1 and HIV-2 Gag synthesis from the full-length RNA. Our results indicate that CTIF associates with HIV-1 Rev through its N-terminal domain and is recruited onto the full-length RNA ribonucleoprotein complex in order to interfere with Gag synthesis. We also demonstrate that CTIF induces the cytoplasmic accumulation of Rev impeding the association of the viral protein with CBP80. We finally show that Rev interferes with the association of CTIF with CBP80 indicating that CTIF and Rev compete for the CBC subunit.

[Five o'clock tea and the risk of metabolic syndrome]. / La ingesta de "once", en reemplazo de la cena, se asocia al riesgo de presentar síndrome metabólico.

BACKGROUND: Seventy four percent of Chileans replaced the traditional dinner for the consumption of "five o'clock tea" (5CT), a mealtime that includes bread and is simliar to western breakfast. The latter favors the intake of unhealthy foods. AIM: To study whether the consumption of "5CT", instead of dinner, could be a risk factor for the development of metabolic syndrome (MetSyn). MATERIAL AND METHODS: Anthropometric parameters, mean blood pressure, lipid profile, thyroid stimulating hormone and fasting glucose were measured in 489 subjects aged 39 ± 12 years (33% women) who attended a primary cardiovascular prevention (CV) program. A 24-hour recall and usual meal times were registered during a dietary interview. To determine the association between the consumption of "5CT" or dinner and the probability of presenting two or more components of MetSyn, we built an odds proportional model adjusted by age and sex. In addition, severity for MetSyn was calculated. RESULTS: Nineteen percent of participants had MetSyn and 39%, two or more MetSyn components. Those who consumed "5CT" instead of dinner, had 54% more probability of having 2 or more MetSyn components (Odds ratio = 1.54, confidence intervals 1.032.32, p = 0.04). Participants who included processed carbohydrates in their last meal had a higher probability of having components of MetSyn. This probability decreased among participants who ate dinner with a low proportion of refined carbohydrates. CONCLUSIONS: Subjects who eat "5CT", instead of dinner as the last meal, have a higher cardiometabolic risk and MetSyn severity.

[Evaluation the American College of Cardiology and American Heart Association Predictive score for cardiovascular diseases]. / Superioridad del nuevo puntaje de riesgo ACC/AHA 2013 por sobre el puntaje de Framingham, en la predicción de riesgo de mortalidad cardiovascular en Santiago.

BACKGROUND: Recently, the American College of Cardiology and American Heart Association (ACC/AHA) proposed a new cardiovascular risk (CV) score. AIM: To evaluate the new risk score (ACC/AHA 2013) in a Chilean population. MATERIAL AND METHODS: Between 2002 and 2014, body mass index (BMI), waist circumference, blood pressure, lipid profile and fasting blood glucose levels were measured and a survey about CV risk factors was responded by 3,284 subjects aged 40 to 79 years (38% females), living in urban Santiago. ACC/AHA 2013, FRAM and Chilean FRAM scores were calculated. All-cause mortality was determined in July 2014 by consulting the Death Registry of the Chilean Identification Service, with an average follow up of 7 ± 3 years. RESULTS: The prevalence of risk factors were 78% for dyslipidemia, 37% for hypertension, 20% for smoking, 7% for diabetes, 20% for obesity and 54% for physical inactivity. The mean FRAM, Chilean FRAM and ACC/AHA scores were 8, 3 and 9%, respectively. During follow-up, 94 participants died and 34 deaths were of cardiovascular cause. Participants who died had a higher prevalence of hypertension (p < 0.01) and diabetes (p < 0. 01) and tended to be older (p = 0.06). The FRAM score for 10 years for deceased and surviving patients was 12 and 8%, respectively (p = NS). The figures for the Chilean FRAM were 5 and 2%, respectively (p = 0.09). The figures for the ACC/AHA 2013 score were 33 and 9%, respectively (p = 0.04). According to receiver operating characteristic curves, ACC/AHA 2013 had a higher area under de curve for CV mortality than FRAM and Chilean FRAM. CONCLUSIONS: The new ACC/AHA 2013 score, is better than traditional FRAM and Chilean FRAM scores in predicting cardiovascular mortality in a low risk population.

[Assessment of adherence to antihypertensive therapy]. / Prevalencia y determinantes de adherencia a terapia antihipertensiva en pacientes de la Región Metropolitana.

BACKGROUND: Lack of adherence with medications is the main cause of antihypertensive treatment failure. AIM: To assess adherence to antihypertensive drugs and its determinants. MATERIAL AND METHODS: The Morinsky-Green questionnaire to determine treatment adherence was applied to 310 hypertensive patients from primary care centers, aged 60 ± 10 years (65% females) in treatment for 4 ± 1 months. Socio-demographic features, use of medications and quality of life using EQ5D questionnaire were also assessed. RESULTS: Twenty percent of patients were diabetic and 19% were smokers. Fifty four percent were adherent to therapy. A higher age and being unemployed were associated with a higher compliance. The main reasons to justify the lack of adherence were forgetting to take the pills in 67% and adverse effects in 10%. Only diastolic pressure was lower in adherent patients, compared with their non-adherent counterparts (78 ± 12 and 81 ± 17 mmHg, respectively p < 0.01). CONCLUSIONS: Only half of hypertensive patients comply with their antihypertensive therapy.

Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents.

Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260.

Crosslinking and mass spectrometry suggest that the isolated NTD domain dimer of Moloney murine leukemia virus integrase adopts a parallel arrangement in solution.

BACKGROUND: Retroviral integrases (INs) catalyze the integration of viral DNA in the chromosomal DNA of the infected cell. This reaction requires the multimerization of IN to coordinate a nucleophilic attack of the 3' ends of viral DNA at two staggered phosphodiester bonds on the recipient DNA. Several models indicate that a tetramer of IN would be required for two-end concerted integration. Complementation assays have shown that the N-terminal domain (NTD) of integrase is essential for concerted integration, contributing to the formation of a multimer through protein-protein interaction. The isolated NTD of Mo-MLV integrase behave as a dimer in solution however the structure of the dimer in solution is not known. RESULTS: In this work, crosslinking and mass spectrometry were used to identify regions involved in the dimerization of the isolated Mo-MLV NTD. The distances between the crosslinked lysines within the monomer are in agreement with the structure of the NTD monomer found in 3NNQ. The intermolecular crosslinked peptides corresponding to Lys 20-Lys 31, Lys 24-Lys 24 and Lys 68-Lys 88 were identified. The 3D coordinates of 3NNQ were used to derive a theoretical structure of the NTD dimer with the suite 3D-Dock, based on shape and electrostatics complementarity, and filtered with the distance restraints determined in the crosslinking experiments. CONCLUSIONS: The crosslinking results are consistent with the monomeric structure of NTD in 3NNQ, but for the dimer, in our model both polypeptides are oriented in parallel with each other and the contacting areas between the monomers would involve the interactions between helices 1 and helices 3 and 4.

[Hypertension in women]. / Hipertensión arterial en la mujer adulta.

The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.

[Carotid intima media thickness and C reactive protein among overweight or obese subjects without metabolic syndrome]. / ¿Sirven los marcadores de riesgo no tradicionales en la diferenciación del riesgo cardiovascular en adultos jóvenes con exceso de peso?

BACKGROUND: Recognizing cardiovascular risk in overweight adults is challenging, as they usually have a low Framingham risk score (FRAM). In these subjects, non-traditional biomarkers could improve risk stratification. AIM: To assess carotid intima media thickness (CIMT) and ultrasensitive C-reactive protein (usCRP) among overweight and obese subjects without metabolic syndrome (MetSyn). SUBJECTS AND METHODS: In 1558 asymptomatic participants (816 women, 45 ± 11 years) we measured body mass index (BMI), waist circumference, blood pressure, lipid profile, blood glucose, FRAM, usCRP and CIMT. For analytical purposes, we divided the subjects in three groups according to BMI and number of ATPIII-MetSyn risk factors (RF): 1) BMI < 25 and < 3RF, 2) BMI ≥ 25 and < 3RF and 3) BMI ≥ 25 and ≥ 3RF. RESULTS: Participants of group 2 (BMI ≥ 25 and < 3RF) had a low FRAM (8%). Compared with participants of group 1, they had a higher CIMT (0.61 ± 0.1 and 0.57 ± 0.09 mm, respectively, p < 0.01) and usCRP (2.1 ± 2.1 and 1.5 ± 1.9 mg/L respectively, p < 0.01). CONCLUSIONS: This study shows that although subjects with overweight/obesity without MetSyn have low cardiovascular risk based on FRAM, they have higher CIMT and usCRP than their normal weight counterparts.

[Association of lipoprotein-associated phospholipase activity A2 with cardiovascular risk factors]. / Niveles de fosfolipasa A2 asociada a lipoproteína en sujetos sin enfermedad coronaria con riesgo cardiovascular variable.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker involved in atherosclerosis and directly associated with cardiovascular events. AIM: To determine Lp-PLA2 levels in asymptomatic subjects with differing cardiovascular risk. MATERIAL AND METHODS: We studied 152 subjects aged 46 ± 11 years (69 women). We recorded traditional cardiovascular risk factors, creatinine, ultrasensitive C-reactive protein, fibrinogen, fasting lipids, blood sugar and activity levels of Lp-PLA2. Cardiovascular risk was classified according to the number of risk factors of each subject (0,1-2 or ≥ 3 risk factors). Besides, we calculated global Framingham risk score. RESULTS: The average Framingham score of participants was 6%. Twenty percent of participants had no risk factors, 46% had 1 or 2 and 34% had ≥ 3. Mean Lp-PLA2 levels were 185 ± 48 nmol/ml/min (201 ± 49 in men and 166 ± 38 in women). Lp-PLA2 correlated significantly (p < 0,05 for all) with non-HDL cholesterol, LDL, HDL, creatinine, waist circumference, body mass index and Framingham risk score. There was no correlation with blood sugar, C-reactive protein, fibrinogen or smoking status. Lp-PLA2 levels were significantly higher according to the number of risk factors: 0 factors: 163 ± 43, 1-2 factors: 185 ± 45 and ≥ 3 factors: 201 ± 47 nmol/ml/min, respectively. Linear regression analysis showed that the best predictor of Lp-PLA2 was non-HDL cholesterol (ß = 0,74; p < 0,0001). CONCLUSIONS: Lp-PLA2 activity increased along with the number of cardiovascular risk factors and was correlated mainly with non -HDL cholesterol.

[Exercise and cardiac rehabilitation in secondary cardiovascular prevention]. / Rehabilitación cardiovascular y ejercicio en prevención secundaria.

Exercise and cardiac rehabilitation are indications with type I A evidence in most secondary cardiovascular prevention guidelines. Rehabilitation programs not only include exercise but also provide integral care and education about cardiovascular risk factors. However there is a paucity of such programs in Chile. Moreover there is a lack of awareness about the benefits of exercise and there is lack of knowledge about the details of exercise prescription in secondary prevention. Therefore, the divulgation of this knowledge is of utmost importance.

Mobile-phone text messaging to promote ideal cardiovascular health in women.

OBJECTIVE: Ideal cardiovascular health (CVH) was developed to promote CVH as a key component of primordial prevention. Mobile short message service (SMS) is useful for improving health behaviours. We aim to test the effectiveness of SMS intervention in women to improve CVH. METHODS: In a single-blinded, randomised, controlled study, 620 women, aged 35-70 years, without cardiovascular disease, were enrolled in SMS intervention versus no SMS. CVH metrics by self-report, and biochemical laboratory, anthropometric and blood pressure measurements were collected during home visits at baseline and 9 months. Women were categorised as having poor (0-2), intermediate (3-4) or ideal (5-7) CVH according to the number of ideal CVH metrics. Participants were randomised 1:1 to SMS intervention versus control. SMS was sent every 5-6 days for 9 months. The primary outcome was the difference in the proportion of women with ideal CVH between SMS and control groups at 9 months. Rates of intermediate CVH, poor CVH and each of the seven ideal CV health metrics at 9 months were key secondary endpoints. RESULTS: At 9 months, there was no significant difference between groups for the primary outcome (16.3% at baseline and 13.3% at 9 months, and 10.1% and 11.1%, in SMS and control groups, respectively, adjusted RR 1.0; 95% CI 0.6 to 1.6). Similarly, there were no significant differences between groups for the key secondary endpoints. SMS had an acceptance rate of 94.9%. CONCLUSIONS: Behavioural SMS intervention did not improve rates of ideal CVH in women, despite being feasible and well received. TRIAL REGISTRATION NUMBER: 6377.

Neutralizing antibodies induced by homologous and heterologous boosters in CoronaVac vaccines in Chile.

OBJECTIVES: To determine the impact of a booster dose on the humoral response in individuals inoculated with a complete schedule of any SARS-CoV-2 vaccine, we evaluated the neutralizing antibody (NAb) titres of homologous or heterologous booster doses over a 90-days period in CoronaVac vaccinees from 3 centres in Santiago, Chile. METHODS: Individuals previously inoculated with 2 doses of CoronaVac (N = 523) were recruited in the context of the REFUERZO clinical trial (NCT04992182) and received either placebo (N = 129), or a booster dose of CoronaVac (N = 134), BNT162b2 (N = 133), or ChAdOx1 (N = 127). Pseudovirus neutralizing antibody titres (pVNT) were determined at baseline (day 0) as well as at days 14, 30, 60, and 90 after booster dose administration. RESULTS: Inoculating a booster dose increases the pVNTs titres at days 14 and 30 in all groups, (13.5- and 12.0-fold increase for the CoronaVac group; 247.0- and 212.3-fold increase for the BTN162b2 group; and 89.1- and 128.1-fold increase for ChAdOx1 at each time point, respectively) with a decline observed at days 60 and 90. However, although pVNTs remained significantly higher for the BTN162b2 and ChAdOx1 groups at days 60 and 90, NAb titres reached baseline levels in the CoronaVac group at 90 days after inoculation. DISCUSSION: A single heterologous booster (BTN162b2 or ChAdOx1) in individuals who completed the CoronaVac primary series resulted in an important increase in NAb titres remaining significantly higher at least for 90 days. These data may directly impact middle- and low-income countries currently using CoronaVac as the main vaccination strategy.

Impact of homologous and heterologous boosters in neutralizing antibodies titers against SARS-CoV-2 Omicron in solid-organ transplant recipients.

Introduction: Booster doses of SARS-CoV-2 vaccines improve seroconversion rates in solid organ transplant recipients (SOTRs) but the impact of homologous and heterologous booster doses in neutralizing antibody (NAb) titers and their ability to interfere with the variant of concern Omicron are not well studied. Methods: We designed a prospective, open-label, observational clinical cohort study. 45 participants received two doses of BNT162b2 or CoronaVac (21-day or 28-day intervals, respectively) followed by a first and second booster with BNT162b2 (5-month apart each) and we analyzed the neutralizing antibody titers against SARSCoV-2 D614G (B.1 lineage) and Omicron (BA.1 lineage). Results: Our results show that SOTRs receiving an initial two-dose scheme of CoronaVac or BNT162b2 generate lower NAbs titers against the ancestral variant of SARS-CoV-2 when compared with healthy controls. Although these NAb titers were further decreased against the SARS-CoV-2 Omicron, a single BNT162b2 booster in both groups was sufficient to increase NAb titers against the variant of concern. More importantly, this effect was only observed in those participants responding to the first two shots but not in those not responding to the initial vaccination scheme. Discussion: The data provided here demonstrate the importance of monitoring antibody responses in immunocompromised subjects when planning booster vaccination programs in this risk group.

COVID-19 lateral flow IgG seropositivity and serum neutralising antibody responses after primary and booster vaccinations in Chile: a cross-sectional study.

BACKGROUND: By June 30, 2022, 92·6% of the Chilean population older than 18 years had received a full primary SARS-CoV-2 vaccine series, mostly with CoronaVac (Sinovac Biotech), and 78·4% had received a booster dose, mostly heterologous with BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (AstraZeneca). We previously reported national seroprevalence data from lateral flow testing of IgG SARS-CoV-2 antibodies up to 16 weeks after primary vaccination. Our aim here was to study IgG seropositivity dynamics up to 30 weeks after primary vaccination and, in CoronaVac recipients, up to 26 weeks after booster vaccination, and to establish the correlation between lateral flow tests and neutralising antibody titres. METHODS: In this cross-sectional study, testing stations for SARS-CoV-2 IgG detection were selected and installed from March 12, 2021, in hotspots in 24 large Chilean cities, and were maintained until March 31, 2022. Individuals voluntarily approaching the testing stations were invited to perform a rapid lateral flow test via a finger prick and complete a questionnaire. Between Aug 12, 2021, and April 1, 2022, volunteers seeking medical care in the Mutual de Seguridad de la Cámara Chilena de la Construcción provided blood samples for lateral flow testing and neutralising antibody studies; inclusion criteria were age at least 18 years, history of complete primary vaccination series with CoronaVac, BNT162b2, or ChAdOx1, or no vaccine, and no previous COVID-19 diagnosis. We tested the difference in IgG positivity across time, and between primary and booster doses, in all eligible participants with complete records, controlling for age, gender, and comorbidities. We also assessed the predictive power of neutralising antibody titres and sociodemographic characteristics on the probability of IgG positive results using multivariable logistic regression. FINDINGS: Of 107 220 individuals recruited at the testing stations, 101 070 were included in our analysis (59 862 [59·2%] women and 41 208 [40·8%] men). 65 902 (65·2%) received primary vaccination series with CoronaVac, 18 548 (18·4%) with BNT162b2, and 606 (0·6%) with ChAdOx1, and 16 014 (15·8%) received no vaccine. Among the 61 767 individuals with a complete primary vaccination series with CoronaVac, 608 (1·0%) received a CoronaVac booster, 10 095 (16·3%) received a BNT162b2 booster, and 5435 (8·8%) received a ChAdOx1 booster. After ChAdOx1 primary vaccination, seropositivity peaked at week 5 after the second dose, occurring in 13 (92·9%, 95% CI 79·4-100·0) of 14 individuals. In participants who received a complete CoronaVac primary series, the decline in seropositivity stabilised at week 18 after the second dose (86 [44·7%, 95% CI 41·8-47·7] of 1087 individuals), whereas after receiving BNT162b2, seropositivity declined slightly by week 25 after the second dose (161 [94·2%, 90·6-97·7] of 171). A lower proportion of individuals who received the CoronaVac primary series and a homologous booster were seropositive (279 [85·6%, 95% CI 81·8-89·4] of 326) by weeks 2-18 than those who received a BNT162b2 booster (7031 [98·6%, 98·4-98·9] of 7128) or a ChAdOx1 booster (2893 [98·0%, 97·5-98·5] of 2953). The correlation between IgG positivity and log of the infectious dose in 50% of neutralising antibodies was moderate, with a sensitivity of 81·4% (95% CI 76·3-86·6) and specificity of 92·5% (73·3-100·0). INTERPRETATION: Dynamic monitoring of IgG positivity to SARS-CoV-2 can characterise antibody waning over time in the absence or presence of booster doses, providing relevant data for the design of vaccination strategies. The correlation between lateral flow test IgG titres and neutralising antibody concentrations suggests that they could be a quick and effective surveillance tool to measure protection against SARS-CoV-2. FUNDING: Instituto Sistemas Complejos de Ingeniería, Subsecretaría de Redes Asistenciales, Ministry of Health, Chile, and Mutual de Seguridad de la Cámara Chilena de la Construcción.