A self-adjuvanted VLPs-based Covid-19 vaccine proven versatile, safe, and highly protective

Vaccination has played a critical role in mitigating COVID-19. Despite the availability of licensed vaccines, there remains a pressing need for improved vaccine platforms that provide high protection, safety, and versatility, while also reducing vaccine costs. In response to these challenges, our aim is to create a self-adjuvanted vaccine against SARS-CoV-2, utilizing Virus-Like Particles (VLPs) as the foundation. To achieve this, we produced bacteriophage (Qβ) VLPs in a prokaryotic system and purified them using a rapid and cost-effective strategy involving organic solvents. This method aims to solubilize lipids and components of the cell membrane to eliminate endotoxins present in bacterial samples. For vaccine formulation, Receptor Binding Domain (RBD) antigens were conjugated using chemical crosslinkers, a process compatible with Good Manufacturing Practice (GMP) standards. Transmission Electron Microscopy (TEM) confirmed the expected folding and spatial configuration of the QβVLPs vaccine. Additionally, vaccine formulation assessment involved SDS-PAGE stained with Coomassie Brilliant Blue, Western blotting, and stereomicroscopic experiments. In vitro and in vivo evaluations of the vaccine formulation were conducted to assess its capacity to induce a protective immune response without causing side effects. Vaccine doses of 20 µg and 50 µg stimulated the production of neutralizing antibodies. In in vivo testing, the group of animals vaccinated with 50 µg of vaccine formulation provided complete protection against virus infection, maintaining stable body weight without showing signs of disease. In conclusion, the QβVLPs-RBD vaccine has proven to be effective and safe, eliminating the necessity for supplementary adjuvants and offering a financially feasible approach. Moreover, this vaccine platform demonstrates flexibility in targeting Variants of Concern (VOCs) via established conjugation protocols with VLPs.

Integrated control strategies for dengue, Zika, and Chikungunya virus infections.

Arboviruses are a major threat to public health in tropical regions, encompassing over 534 distinct species, with 134 capable of causing diseases in humans. These viruses are transmitted through arthropod vectors that cause symptoms such as fever, headache, joint pains, and rash, in addition to more serious cases that can lead to death. Among the arboviruses, dengue virus stands out as the most prevalent, annually affecting approximately 16.2 million individuals solely in the Americas. Furthermore, the re-emergence of the Zika virus and the recurrent outbreaks of chikungunya in Africa, Asia, Europe, and the Americas, with one million cases reported annually, underscore the urgency of addressing this public health challenge. In this manuscript we discuss the epidemiology, viral structure, pathogenicity and integrated control strategies to combat arboviruses, and the most used tools, such as vaccines, monoclonal antibodies, treatment, etc., in addition to presenting future perspectives for the control of arboviruses. Currently, specific medications for treating arbovirus infections are lacking, and symptom management remains the primary approach. However, promising advancements have been made in certain treatments, such as Chloroquine, Niclosamide, and Isatin derivatives, which have demonstrated notable antiviral properties against these arboviruses in vitro and in vivo experiments. Additionally, various strategies within vector control approaches have shown significant promise in reducing arbovirus transmission rates. These encompass public education initiatives, targeted insecticide applications, and innovative approaches like manipulating mosquito bacterial symbionts, such as Wolbachia. In conclusion, combatting the global threat of arbovirus diseases needs a comprehensive approach integrating antiviral research, vaccination, and vector control. The continued efforts of research communities, alongside collaborative partnerships with public health authorities, are imperative to effectively address and mitigate the impact of these arboviral infections on public health worldwide.

Vaccines against Emerging and Neglected Infectious Diseases: An Overview.

Neglected Tropical Diseases (NTDs) are a group of diseases that are highly prevalent in tropical and subtropical regions, and closely associated with poverty and marginalized populations. Infectious diseases affect over 1.6 billion people annually, and vaccines are the best prophylactic tool against them. Along with NTDs, emerging and reemerging infectious diseases also threaten global public health, as they can unpredictably result in pandemics. The recent advances in vaccinology allowed the development and licensing of new vaccine platforms that can target and prevent these diseases. In this work, we discuss the advances in vaccinology and some of the difficulties found in the vaccine development pipeline for selected NTDs and emerging and reemerging infectious diseases, including HIV, Dengue, Ebola, Chagas disease, malaria, leishmaniasis, zika, and chikungunya.

VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants.

Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrating convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, optimized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology.

Circadian chronotypes among wild-captured west Andean octodontids.

Rest activity pattern was studied in wild-captured males of Octodon degus (n=9), Octodon bridgesi (n=3), and Spalacopus cyanus (n=6) (Rodentia: Octodontidae). Ten-minute resolution actograms were constructed from data obtained by an automated acquisition system. After two months of habituation to a stable light-dark schedule, recordings were performed in isolation chambers under a 12: 12 Light Dark schedule. A free-running period (constant darkness) was recorded for O. bridgesi and S. cyanus. O. degus displayed a crepuscular pattern of rest activity rhythm. Entrained O. bridgesi and S. cyanus displayed nocturnal preference, with rest anticipating light phase and without crepuscular activity bouts. Under constant darkness, active phase occurred at subjective night in O. bridgesi and S. cyanus. Wild-captured O. bridgesi and S. cyanus possess a circadian driven nocturnal preference, while wild O. degus displays a crepuscular profile. Diurnal active phase preference of wild S. cyanus colonies observed in the field could not be explained solely by photic entrainment, since social and/or masking processes appear to be operative. The genus Octodon includes species with diverse chronotypes. We propose that crepuscular diurnal pattern observed in O. degus is a recent acquisition among the octodontid lineage.

Circadian chronotypes among wild-captured west Andean octodontids

Rest activity pattern was studied in wild-captured males of Octodon degus (n=9), Octodon bridgesi (n=3), and Spalacopus cyanus (n=6) (Rodentia: Octodontidae). Ten-minute resolution actograms were constructed from data obtained by an automated acquisition system. After two months of habituation to a stable light-dark schedule, recordings were performed in isolation chambers under a 12: 12 Light Dark schedule. A free-running period (constant darkness) was recorded for O. bridgesi and S. cyanus. O. degus displayed a crepuscular pattern of rest activity rhythm. Entrained O. bridgesi and S. cyanus displayed nocturnal preference, with rest anticipating light phase and without crepuscular activity bouts. Under constant darkness, active phase occurred at subjective night in O. bridgesi and S. cyanus. Wild-captured O. bridgesi and S. cyanus possess a circadian driven nocturnal preference, while wild O. degus displays a crepuscular profile. Diurnal active phase preference of wild S. cyanus colonies observed in the field could not be explained solely by photic entrainment, since social and/or masking processes appear to be operative. The genus Octodon includes species with diverse chronotypes. We propose that crepuscular diurnal pattern observed in O. degus is a recent acquisition among the octodontid lineage.

Ocorrência natural de fumonisinas no milho produzido pelo sistema tradicional de cultivo, em comunidades de agricultura familiar do Estado de Mato Grosso / Ocurrence of fumonisins in maize in field communities from the Central South of State of Mato Grosso

O estudo foi realizado na região centro-sul de Mato Grosso, entre 14º e 16º de latitude Sul e 55º e 57º de longitude Oeste, em 35 propriedades que constituíram nossa base amostral. Dessa base amostral foram concebidos 4 tratamentos experimentais (T1,T2,T3,T4), representados pelas correspondentes amostras, tomadas a intervalos de 30 a 60 dias entre elas, no período de abril a agosto de 1999, totalizando 140 amostras. Os resultados relativos ao teor de umidade apresentaram uma tendência decrescente dos tratamentos T1 a T4, da magnitude de 0,76 ± 0,014 a 0,47 ± 0,009, para atividade de água e de 12,81 por cento ± 0,44 a 7,52 por cento ± 0,21 para teor percentual de água, abaixo, portanto, daqueles considerados adequados para a produção de fumonisinas.

Ocorrência de aflatoxinas em milho produzido pelo sistema tradicional de cultivo, em comunidades de agricultura familiar, no Estado de Mato Grosso / Occurrence of aflatoxin in maize in field communities from the Central South of State of Mato Grosso

Foi realizado na regiäo centro-sul de Mato Grosso, entre 14§ e 16§ de latitude sul e 55§ e 57§ de longitude oeste, em 35 propriedades que constituíram nossa base amostral. Dessa base amostral foram concebidos 4 tratamentos experimentais (T1, T2, T3, T4), representados pelas correspondentes amostras, tomadas a intervalos de 30 e 60 dias entre elas, no período de abril a agosto de 1999, totalizando 140 amostras. Os resultados relativos ao teor de umidade apresentaram uma tendência decrescente dos tratamentos T1 a T4, da magnitude de 0,76 ñ 0,014 a 0,47 ñ 0,009, para atividade de água e de 12,81 por cento ñ 0,44 a 7,52 por cento ñ 0,21 para teor percentual de água, abaixo, portanto, daqueles considerados adequados para a produçäo de aflatoxinas. Os valores percentuais médios de gräos avariados, para os mesmos tratamentos (T1; T2; T3 e T4), ofereceram, aparentemente, uma tendência crescente, que oscilou entre 9,68 por cento e 19,74 por cento, evidenciando que, além do comprometimento inicial, o período de estocagem propiciou condiçöes favoráveis para a ocorrência de danos expressivos. Por ocasiäo da primeira tomada de amostras (T1), 10/35 (28,57 por cento revelaram, pela técnica imunoenzimática de competiçäo direta, a presença de aflatoxinas (3 2 ppb), com um valor médio de 12,35 ppb. A maior concentraçäo encontrada foi de 142,5 ppb, e das 10 amostras positivas, 4 (11,43 por cento) apresentaram concentraçöes superiores a 20 ppb, limite máximo de aceitaçäo para o consumo. Nas demais tomadas (T2; T3 e T4) a freqüência foi de 12 (34,29 por cento), 15 (42,86 por cento), e 27 (77,14 por cento) e destas, 6 (17,14 por cento), 8 (22,86 por cento) e 6 (17,14 por cento) em concentraçöes superiores a 20 ppb. Os maiores níveis de aflatoxinas encontrados foram 431 ppb; 248 ppb e 379 ppb para T2; T3 e T4 e as concentraçöes médias para estes tratamentos foram respectivamente, 22,94 ppb; 26,99 ppb e 34,17 ppb, todas superiores ao limite máximo admitido para consumo. A comparaçäo das formas de conservaçäo do milho em T4 (lavoura ou paiol), com os respectivos níveis de dano e presença de aflatoxinas revelou que as amostras colhidas, ainda na lavoura, apresentaram um nível de dano de 15,81 por cento, contra 23,05 por cento das amostras estocadas em paiós. Das 16 amostras colhidas de lavouras, 12 (75 por cento) foram positivas para aflatoxinas (3 2 ppb), contra 15 (78,95 por cento) do grupo de 19 amostras colhidas em paiós.