Neutralizing antibody response after immunization with a COVID-19 bivalent vaccine: Insights to the future.

The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.

The COVID-19 Humoral Immunological Status Induced by CoronaVac and AstraZeneca Vaccines Significantly Benefits from a Booster Shot with the Pfizer Vaccine.

A third vaccine dose against COVID-19 is already a reality in some countries around the world. In this study, we aimed to evaluate the effectiveness of the Brazilian immunization policy for COVID-19, which involves a booster shot. Participants (n = 210) provided serum samples, which were subjected to enzyme-linked immunosorbent assay (ELISA). Immunological profiles were defined as individuals with or without previous SARS-CoV-2 infection who received at least one vaccine dose in the immunization regimens of AstraZeneca, CoronaVac, or CoronaVac plus a booster shot with Pfizer. In addition, nonvaccinated/infected individuals were also included. As main results, we observed that the numbers of infected individuals were significantly reduced among those who were vaccinated, even with one dose. This result indicates that vaccines are highly protective against COVID-19. However, we observed a significant tendency of serum level decreases of specific antibodies over the time after the second dose. In contrast, the booster shot with the Pfizer vaccine after a CoronaVac immunization regimen showed a significant increase in the specific SARS-CoV-2 IgG serum levels. Moreover, we found that vaccination induced a significantly higher humoral immunological status than only the natural infection with SARS-CoV-2. Collectively, results presented here indicate that vaccines are necessary to induce a robust immunological status, which is maintained, restored, or even improved by booster shots. IMPORTANCE COVID-19 continues to spread around the world despite significant progress in vaccine distribution and population immunity. The dynamics of the antiviral antibody response postvaccination is critical to evaluate vaccine effectiveness across different vaccine platforms and over time. In this study, we evaluate the serum levels of antiviral antibodies in patients from Brazil that received either the CoronaVac or the AstraZeneca vaccine. We found that antibody levels wane over time, vaccines induce protective immunity, and humoral immunity is enhanced with a third vaccine dose. This study reveals that the COVID-19 humoral immunological status induced by vaccines significantly benefits from a booster shot.

The third vaccine dose significantly reduces susceptibility to the B.1.1.529 (Omicron) SARS-CoV-2 variant.

The main coronavirus disease 2019 (COVID-19) vaccine formulations used today are mainly based on the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein as an antigen. However, new virus variants capable of escaping neutralization activity of serum antibodies elicited in vaccinated individuals have emerged. The Omicron (B.1.1.529) variant caused epidemics in regions of the world in which most of the population has been vaccinated. In this study, we aimed to understand what determines individual's susceptibility to Omicron in a scenario of extensive vaccination. For that purpose, we collected nasopharynx swab (n = 286) and blood samples (n = 239) from flu-like symptomatic patients, as well as their vaccination history against COVID-19. We computed the data regarding vaccine history, COVID-19 diagnosis, COVID-19 serology, and viral genome sequencing to evaluate their impact on the number of infections. As main results, we showed that vaccination in general did not reduce the number of individuals infected by Omicron, even with an increased immune response found among vaccinated, noninfected individuals. Nonetheless, we found that individuals who received the third vaccine dose showed significantly reduced susceptibility to Omicron infections. A relevant evidence that support this finding was the higher virus neutralization capacity of serum samples of most patients who received the third vaccine dose. In summary, this study shows that boosting immune responses after a third vaccine dose reduces susceptibility to COVID-19 caused by the Omicron variant. Results presented in this study are useful for future formulations of COVID-19 vaccination policies.

Glioma Pericytes Promote Angiogenesis by Producing Periostin.

Glioma is the prevalent aggressive primary brain tumor, with a very poor prognosis. The absence of advanced understanding of the roles played by the cells within the glioma microenvironment limits the development of effective drugs. A recent study indicates that periostin expressed by pericytes is crucial for glioma angiogenesis. Here, we describe succinctly the results and implications of this discovery in what we know about pericytes within the glioma microenvironment. The emerging knowledge from this work will benefit the development of therapies for gliomas.

First description of a multisystemic and lethal SARS-CoV-2 variant of concern P.1 (Gamma) infection in a FeLV-positive cat.

BACKGROUND: Phylogenetic studies indicate bats as original hosts of SARS-CoV-2. However, it remains unclear whether other animals, including pets, are crucial in the spread and maintenance of COVID-19 worldwide. METHODS: In this study, we analyzed the first fatal case of a SARS-CoV-2 and FeLV co-infection in an eight-year-old male cat. We carried out a clinical evaluation and several laboratory analyses. RESULTS: As main results, we observed an animal presenting severe acute respiratory syndrome and lesions in several organs, which led to the animal's death. RT-qPCR analysis showed a SARS-CoV-2 as the causative agent. The virus was detected in several organs, indicating a multisystemic infection. The virus was found in a high load in the trachea, suggesting that the animal may have contribute to the transmission of the virus. The whole-genome sequencing revealed an infection by SARS-CoV-2 Gamma VOC (P.1), and any mutations indicating host adaptation were observed. CONCLUSION: Our data show that FeLV-positive cats are susceptible to SARS-CoV-2 infection and raise questions about the potential of immunocompromised FeLV-positive cats to act as a reservoir for SARS-CoV-2 new variants.

The History of Methicillin-Resistant Staphylococcus aureus in Brazil.

Since the emergence of MRSA in the 1960s, a gradual increase in infections by resistant bacteria has been observed. Clinical manifestations may vary from brand to critical condition due to host risk factors, as well as pathogen virulence and resistance. The high adaptability and pathogenic profile of MRSA clones contributed to its spread in hospital and community settings. In Brazil, the first MRSA isolates were reported in the late 1980s, and since then different genetic profiles, such as the Brazilian epidemic clone (BEC) and other clones considered a pandemic, became endemic in the Brazilian population. Additionally, Brazil's MRSA clones were shown to be able to transfer genes involved in multidrug resistance and enhanced pathogenic properties. These events contributed to the rise of highly resistant and pathogenic MRSA. In this review, we present the main events which compose the history of MRSA in Brazil, including numbers and locations of isolation, as well as types of staphylococcal cassette chromosome mec (SCCmec) found in the Brazilian territory.

In silico design of a Zika virus non-structural protein 5 aiming vaccine protection against zika and dengue in different human populations.

BACKGROUND: The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. Recently, it was shown that previous humoral immunity to DENV enhances ZIKV replication in vitro, which may lead to more severe forms of the disease. Thus, traditional approaches of vaccine development aiming to control viral infection through neutralizing antibodies may induce cross-reactive enhancing antibodies. In contrast, cellular immune response was shown to be capable of controlling DENV infection independently of antibodies. The aim of the present study was to design a flavivirus NS5 protein capable of inducing a cellular immune response against DENV and ZIKV. METHODS: A consensus sequence of ZIKV NS5 protein was designed among isolates from various continents. Epitopes were predicted for the most prevalent alleles of class I and II HLA in the Brazilian population. Then, this epitopes were analyzed with regard to their conservation, population coverage and distribution along the whole antigen. RESULTS: Nineteen epitopes predicted to be more reactive (percentile rank <1) and 100% conserved among ZIKV and DENV serotypes were selected. The distribution of such epitopes along the protein was shown on a three-dimensional model and population coverage was calculated for different regions of the world. The designed protein was predicted to be stable and the distribution of selected epitopes was shown to be homogeneous along domains. The population coverage of selected epitopes was higher than 50% for most of tropical areas of the world. CONCLUSION: Such results indicate that the proposed antigen has the potential to induce protective cellular immune response to ZIKV and DENV in different human populations of the world.

Gene therapy with the caspase activation and recruitment domain reduces the ocular inflammatory response.

Inflammation is a key component of chronic and acute diseases of the eye. Our goal is to test anti-inflammatory genes delivered by an adeno-associated virus (AAV) vector as potential treatments for retinal inflammation. We developed a secretable and cell penetrating form of the caspase activation and recruitment domain (CARD) from the apoptosis-associated speck-like protein containing a CARD (ASC) gene that binds caspase-1 and inhibits its activation by the inflammasome. The secretion and cell penetration characteristics of this construct were validated in vitro by measuring its effects on inflammasome signaling in a monocyte cell line and in an retinal pigmented epithelium (RPE) cell line. This vector was then packaged as AAV particles and tested in the endotoxin-induced uveitis mouse model. Gene expression was monitored one month after vector injection by fluorescence fundoscopy. Ocular inflammation was then induced by injecting lipopolysaccharide into the vitreous and was followed by enucleation 24 hours later. Eyes injected with the secretable and cell penetrating CARD AAV vector had both a significantly lower concentration of IL-1ß as well as a 64% reduction in infiltrating cells detected in histological sections. These results suggest that anti-inflammatory genes such as the CARD could be used to treat recurring inflammatory diseases like uveitis or chronic subacute inflammations of the eye.

Immune targets to stop future SARS-CoV-2 variants.

IMPORTANCE: The emergence of SARS-CoV-2 had a major impact across the world. It is true that the collaboration of scientists from all over the world resulted in a rapid response against COVID-19, mainly with the development of vaccines against the disease. However, many viral genetic variants that threaten vaccines have emerged. Our study reveals highly conserved antigenic regions in the vaccines have emerged. Our study reveals highly conserved antigenic regions in the spike protein in all variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) as well as in the wild-type virus. Such immune targets can be used to fight future SARS-CoV-2 variants.

Co-circulation of Chikungunya virus, Zika virus, and serotype 1 of Dengue virus in Western Bahia, Brazil.

Chikungunya, mayaro, dengue, zika, and yellow fever are mosquito-borne viral diseases caused, respectively, by Chikungunya virus, Mayaro virus (CHIKV and MAYV, respectively: Togaviridae: Alphavirus), Dengue virus, Zika virus, and Yellow fever virus (DENV, ZIKV, and YFV, respectively: Flaviviridae: Flavivirus). These viruses have an important epidemiological impact worldwide, especially in Brazil. Western Bahia is one of the less studied regions in that country regarding the circulation of these pathogens. In this study, we aimed to apply molecular biology assays to better know the mosquito-borne viruses circulating in Barreiras and Luís Eduardo Magalhães, two main cities of Western Bahia. From March to June 2021, we enrolled 98 patients with the clinical diagnosis of dengue. Personal information (gender and age) were retrieved at the moment of enrollment. Serum samples were obtained from volunteers and used in molecular detection of CHIKV, MAYV, DENV, ZIKV, and YFV by reverse transcription followed by real-time polymerase chain reaction as well as in genome sequencing aiming phylogenetic analysis. As the main result, we found that from the 98 patients 45 were infected by CHIKV, 32 were infected by serotype 1 of DENV (DENV-1) and six were infected by ZIKV, while 15 were negative for all arboviruses tested. In addition, phylogenetic analysis revealed that all CHIKV-positive samples were of the East/Central/South African (ECSA) genotype, while all DENV-1-positive samples were of the V genotype. These results clearly show that epidemiological surveillance cannot be based only on clinical evaluations. Laboratory diagnosis is important in arbovirus infection that are prevalent in a particular area. These findings also demonstrate the co-circulation of many arboviruses in Western Bahia in 2021.