Protein-based Nanoparticle Vaccine Approaches Against Infectious Diseases.

The field of vaccine development has seen an increase in the number of rationally designed technologies that increase effectiveness against vaccine-resistant pathogens, while not compromising safety. Yet, there is still an urgent need to expand and further understand these platforms against complex pathogens that often evade protective responses. Nanoscale platforms have been at the center of new studies, especially in the wake of the coronavirus disease 2019 (COVID-19), with the aim of deploying safe and effective vaccines in a short time period. The intrinsic properties of protein-based nanoparticles, such as biocompatibility, flexible physicochemical characteristics, and variety have made them an attractive platform against different infectious disease agents. In the past decade, several studies have tested both lumazine synthase-, ferritin-, and albumin-based nanoplatforms against a wide range of complex pathogens in pre-clinical studies. Owed to their success in pre-clinical studies, several studies are undergoing human clinical trials or are near an initial phase. In this review we highlight the different protein-based platforms, mechanisms of synthesis, and effectiveness of these over the past decade. In addition, some challenges, and future directions to increase their effectiveness are also highlighted. Taken together, protein-based nanoscaffolds have proven to be an effective means to design rationally designed vaccines, especially against complex pathogens and emerging infectious diseases.

Parameters to Predict the Outcome of Severe and Critical COVID-19 Patients when Admitted to the Hospital.

Manifestations of COVID-19 are diverse and range from asymptomatic to severe, critical illness and death. Cases requiring hospital care (in severe and critical illnesses) are associated with comorbidities and hyperactivation of the immune system. Therefore, in this exploratory observational study, we analyzed which parameters are associated with mortality. We evaluated: demographic characteristics (age, sex and comorbidities), laboratory data (albumin, leukocytes, lymphocytes, platelets, ferritin), days of hospital stay, interleukins (IL-2, IL-6, IL-7, IL-10, IL-17) and sP-selectin in 40 Mexican patients admitted to medical emergencies with a confirmed diagnosis of COVID-19, a complete clinical record, and who signed the informed consent. Twenty severe (they required intermediate care with non-invasive ventilation) and twenty critically ill patients (they required mechanical ventilation) were classified, and these were subsequently compared with healthy and recovered subjects. A significant difference was found between the hospitalized groups in the parameters of age, ferritin, days of hospital stay and death with p values = 0.0145, p = 0.0441, p = 0.0001 and p = 0.0001, respectively. In the determination of cytokines and P-selectin, a significant difference was found between the following groups: recovered patients and healthy volunteers compared with hospitalized patients in severe and critical condition. Importantly, IL-7 remained elevated one year later in recovered patients. Taken together, these values determined at the time of hospital admission could be useful to monitor patients closely and evaluate in-hospital progress, hospital discharge, and out-of-hospital progress.

Chapter 7 - Viral-vectored vaccines against SARS-CoV-2

COVID-19 is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The worldwide spread of COVID-19 has caused significant morbidity and mortality, and virus control has been challenging due to the lack of specific therapeutics or vaccines. Efficacious COVID-19 vaccines are essential to control the current pandemic and thus development of a safe and effective COVID-19 vaccine is a public health priority. Development of COVID-19 vaccines based on next-generation platforms have progressed through the clinical trials at unprecedented fast pace supported by international collaborations prompting a new era in vaccinology. In this chapter, we discuss about the rapid COVID-19 vaccine development, in comparison to other vaccines against newly emerging diseases. Next, we discuss about the classical versus next-generation platforms used for COVID-19 vaccines with particular attention to the leading viral-vectored vaccines in the latest clinical trials.

A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial.

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.

A bioinformatic prediction of antigen presentation from SARS-CoV-2 spike protein revealed a theoretical correlation of HLA-DRB1*01 with COVID-19 fatality in Mexican population: An ecological approach.

SARS-CoV-2 infection is causing a pandemic disease that is reflected in challenging public health problems worldwide. Human leukocyte antigen (HLA)-based epitope prediction and its association with disease outcomes provide an important base for treatment design. A bioinformatic prediction of T cell epitopes and their restricted HLA Class I and II alleles was performed to obtain immunogenic epitopes and HLA alleles from the spike protein of the severe acute respiratory syndrome coronavirus 2 virus. Also, a correlation with the predicted fatality rate of hospitalized patients in 28 states of Mexico was done. Here, we describe a set of 10 highly immunogenic epitopes, together with different HLA alleles that can efficiently present these epitopes to T cells. Most of these epitopes are located within the S1 subunit of the spike protein, suggesting that this area is highly immunogenic. A statistical negative correlation was found between the frequency of HLA-DRB1*01 and the fatality rate in hospitalized patients in Mexico.

SARS-CoV-2 mutations and where to find them: an in silico perspective of structural changes and antigenicity of the spike protein.

Communicated by Ramaswamy H. Sarma.

COVID-19 vaccines: breaking record times to first-in-human trials.

The twenty-first century has come with a new era in vaccinology, in which recombinant genetic technology has contributed to setting an unprecedented fast pace in vaccine development, clearly demonstrated during the recent COVID-19 pandemic.