Effectiveness of the CoronaVac® vaccine in a region of the Colombian Amazon, was herd immunity achieved?

Introduction Currently, more than 4.5 billion doses of SARS-CoV-2 vaccines have been applied worldwide. However, some developing countries are still a long way from achieving herd immunity through vaccination. In some territories, such as the Colombian Amazon, mass immunization strategies have been implemented with the CoronaVac® vaccine. Due to its proximity to Brazil, where one of the variants of interest of SARS-CoV-2 circulates. Objective To determine the effectiveness of the CoronaVac® vaccine in a population of the Colombian Amazon. Methods Between February 24, 2021, and August 10, 2021, a descriptive observational study was carried out in which a population of individuals over 18 years of age immunized with two doses of the CoronaVac® vaccine was evaluated. The study site was in the municipality of Mitú, Vaupés, in southeastern Colombia, a region located in the Amazon bordering Brazil. Results. 99% of the urban population of the Mitú municipality were vaccinated with CoronaVac®. To date, 5.7% of vaccinated individuals have become ill, and only 0.1% of these require hospitalization. One death was attributable to COVID-19 has been reported among vaccinated individuals, and the vaccine has shown 94.3% effectiveness against mild disease and 99.9% against severe infection. Conclusions The herd immunity achieved through mass vaccination in this population has made it possible to reduce the rate of complicated cases and mortality from COVID-19 in this region of the Colombian Amazon. Highlights CoronaVac® has shown 94.3% effectiveness against mild disease and 99.9% against severe infection in this indigenous population. CoronaVac® reduces the mortality rate from 2.2% in 2020 to 0.22% in 2021. The herd immunity was achieved through mass vaccination in this region of the Colombian Amazon.

Nosocomial RSV-related in-hospital mortality in children <5 years: a global case series

Background According to the World Health Organization the global burden of nosocomial infections is poorly characterized as surveillance systems for nosocomial infection are lacking. Nosocomial infections occur at higher rates in low- and lower-middle-income countries (LMICs) than in high-income countries (HICs). Current global RSV burden estimates are largely based on community-acquired disease. We aimed to characterize children with nosocomial RSV-related mortality and to understand the potential impact of RSV immunization strategies. Methods RSV GOLD is a global registry of children younger than 5 years who died with laboratory-confirmed RSV infection. We compared clinical and demographic characteristics of children with nosocomial and community-acquired RSV in-hospital mortality. Results We included 231 nosocomial and 931 community-acquired RSV-related in-hospital deaths from 65 countries. Median age at death was similar for both groups (5.4 vs 6 months). As expected, a higher proportion of children with nosocomial infection had comorbidities (87% vs 57%; p<0.001) or was born preterm (46% vs 24%; p<0.001) than children with community-acquired infection. The proportion of nosocomial deaths among all RSV deaths was lower in LMICs than in upper-middle-income countries (UMICs) and HICs (12% vs 18% and 26%, respectively). Conclusions This is the first global case series of children dying with nosocomial RSV infection. Future infant-targeted immunization strategies can prevent the majority of nosocomial RSV-related deaths. Although nosocomial RSV deaths are expected to occur at highest rates in LMICs, the number of reported nosocomial RSV deaths was low in these countries. Hospital-based surveillance is needed to capture the full burden of nosocomial RSV mortality in LMICs.

Characterizing the transmission patterns of seasonal influenza in Italy: lessons from the last decade

Background Despite thousands of influenza cases annually recorded by surveillance systems around the globe, estimating the transmission patterns of seasonal influenza is challenging. Methods We develop an age-structured mathematical model to influenza transmission to analyze ten consecutive seasons (from 2010 to 2011 to 2019–2020) of influenza epidemiological and virological data reported to the Italian surveillance system. Results We estimate that 18.4–29.3% of influenza infections are detected by the surveillance system. Influenza infection attack rate varied between 12.7 and 30.5% and is generally larger for seasons characterized by the circulation of A/H3N2 and/or B types/subtypes. Individuals aged 14 years or less are the most affected age-segment of the population, with A viruses especially affecting children aged 0–4 years. For all influenza types/subtypes, the mean effective reproduction number is estimated to be generally in the range 1.09–1.33 (9 out of 10 seasons) and never exceeding 1.41. The age-specific susceptibility to infection appears to be a type/subtype-specific feature. Conclusions The results presented in this study provide insights on type/subtype-specific transmission patterns of seasonal influenza that could be instrumental to fine-tune immunization strategies and non-pharmaceutical interventions aimed at limiting seasonal influenza spread and burden.

Broad anti-SARS-CoV-2 antibody immunity induced by heterologous ChAdOx1/mRNA-1273 prime-boost vaccination

Heterologous prime-boost immunization strategies have the potential to augment COVID-19 vaccine efficacy and address ongoing vaccine supply challenges. Here, we longitudinally profiled SARS-CoV-2 spike (S)-specific serological and memory B cell (MBC) responses in individuals receiving either homologous (ChAdOx1:ChAdOx1) or heterologous (ChAdOx1:mRNA-1273) prime-boost vaccination. Heterologous mRNA booster immunization induced significantly higher serum neutralizing antibody and MBC responses compared to homologous ChAdOx1 boosting. Specificity mapping of circulating S-specific B cells revealed that mRNA-1273 booster immunization dramatically immunofocused ChAdOx1-primed responses onto epitopes expressed on prefusion-stabilized S. Monoclonal antibodies isolated from mRNA-1273-boosted participants displayed higher binding affinities and increased breadth of reactivity against variants of concern (VOCs) relative to those isolated from ChAdOx1-boosted participants. Overall, the results provide fundamental insights into the B cell response induced by ChAdOx1 and a molecular basis for the enhanced immunogenicity observed following heterologous mRNA booster vaccination.

A recombinant SARS-CoV-2 RBD antigen expressed in insect cells elicits immunogenicity and confirms safety in animal models

COVID-19 pandemic has accelerated the development of vaccines against its etiologic agent, SARS-CoV-2. However, the emergence of new variants of the virus requires new immunization strategies in addition to the current vaccines approved for human administration. In the present report, the immunological and safety evaluation in mice and hamsters of a subunit vaccine based on the RBD sub-domain with two adjuvants of oil origin is described. The RBD protein was expressed in insect cells and purified by chromatography until >95% purity. The protein was shown to have the appropriate folding as determined by ELISA and flow cytometry binding assays to its receptor, as well as by its detection by hamster immune anti-S1 sera under non-reducing conditions. In immunization assays in mice and hamsters, the purified RBD formulated with adjuvants based on oil-water emulsifications and squalene was able to stimulate specific neutralizing antibodies and confirm the secretion of IFN-γ after stimulating spleen cells with the purified RBD. The vaccine candidate was shown to be safe, as demonstrated by the histopathological analysis in lungs, liver and kidney. These results demonstrate the potential of the purified RBD administered with adjuvants through an intramuscular route, to be evaluated in a challenge against SARS-CoV-2 and determine its ability to confer protection against infection.

Correlation and trust mechanisms-based rumor propagation model in complex social networks

In real life, the process of rumor propagation is influenced by many factors. The complexity and uncertainty of human psychology make the diffusion model more challenging to depict. In order to establish a comprehensive propagation model, in this paper, we take some psychological factors into consideration to mirror rumor propagation. Firstly, we use the Ridenour model to combine the trust mechanism with the correlation mechanism and propose a modified rumor propagation model. Secondly, mean-field equations which describe the dynamics of the modified SIR model on homogenous and heterogeneous networks are derived. Thirdly, a steady-state analysis is conducted for the spreading threshold and the final rumor size. Fourthly, we investigate rumor immunization strategies and obtain immunization thresholds. Next, simulations on different networks are carried out to verify the theoretical results and the effectiveness of the immunization strategies. The results indicate that the utilization of trust and correlation mechanisms leads to a larger final rumor size and a smaller terminal time. Moreover, different immunization strategies have disparate effectiveness in rumor propagation.

Modelling optimal vaccination strategies against Covid-19 in a context of Gamma variant predominance in Brazil

Brazil experienced moments of collapse in its health system throughout 2021, driven by a timid initial vaccination strategy against Covid-19, combined with the emergence of variants of interest (VOC). Mathematical modelling has been used to subsidize decision-makers in public health planning. Considering the vaccine products available, effectiveness estimates, the emergence of Gamma as the predominant VOC circulating in 2021, and national estimated doses available for the next several months, we developed a Markov-chain mathematical modelling approach to evaluate optimal strategies for Covid-19 vaccination in Brazil in terms of Covid deaths averted. Our main findings are that in order to reach higher vaccination impact in Brazil, Covid-19 immunization strategies should include recovering vaccination coverage rates in high-risk groups reaching higher coverage; expanding vaccination to younger age groups should be considered only after ensuring at least 80% coverage in older age groups; reducing the interval between doses of AZD1222 from 12 to 8 weeks. We also demonstrate that the latter is only feasible if accompanied by an increase in vaccine supply of at least 50% in the next six month period.

Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients

There is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin’s lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT50) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT50 levels, with 50-60% of them below the detection limit; (3) mean NT50 levels in patients with CLL and NHL was ~2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT50 levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.

Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice

Background Pemphigus vulgaris (PV) is a rare autoimmune blistering disease characterized by the development of autoantibodies targeting desmoglein (Dsg) 3, but also against Dsg1 in mucocutaneous disease. Given that existing PV animal models only recapitulate aspects of the disease, we aimed to establish a more comprehensive disease model based on the immunization of mice with PV autoantigen(s). Methods The following immunization strategies were tested: (i) C57Bl/6J, B6.SJL-H2s C3c/1CyJ, DBA2/J, or SJL/J mice were immunized with recombinant murine Dsg3 (mDsg3), (ii) DBA2/J and SJL/J mice were immunized with mDsg3 and additionally injected a single non-blister inducing dose of exfoliative toxin A (ETA), and (iii) DBA2/J and SJL/J mice were immunized with human Dsg (hDsg) 1 and 3. Results Despite the induction of autoantibodies in each immunization protocol, the mice did not develop a clinical phenotype. Tissue-bound autoantibodies were not detected in the skin or mucosa. Circulating autoantibodies did not bind to the native antigen in indirect immunofluorescence microscopy using monkey esophagus as a substrate. Conclusion Immunization with PV autoantigens induced non-pathogenic Dsg1/3 antibodies, but did not cause skin/mucous membrane disease in mice. These findings, confirmed by failure of binding of the induced autoantibodies to their target in the skin, suggest that the autoantibodies which were formed were unable to bind to the conformational epitope present in vivo.