The potential of plant-made vaccines to fight picornavirus.

INTRODUCTION: Several Picornaviruses are pathogens that generate serious problems for human and animal health worldwide. Vaccination is an attractive approach to fight against picornaviruses. In this regard, the development of low-cost vaccines is a priority to ensure coverage; especially in developing and low-income countries. In this context, plant-made vaccines are a convenient technology since plant cells are low-cost bioreactors capable of producing complex antigens that preserve their antigenic determinants; moreover, they can serve as biocapsules to achieve oral delivery. AREAS COVERED: In the present review the advances in the development of plant-made vaccines against picornaviruses are summarized and placed in perspective. The main diseases that have been targeted using this approach include Poliovirus, Food and mouth disease virus, Hepatitis A virus, and Enterovirus 71. EXPERT OPINION: Several vaccine candidates against picornavirus have been characterized at the preclinical level; with many of them capable of inducing humoral and cellular responses that led to neutralization of pathogens when evaluated in vitro and test animal challenge assays. Plant-made vaccines are a promise to fight picornaviruses; especially in the developing world where limited resources hamper vaccination coverage. A critical analysis of the road ahead for this technology is provided.

Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.

Prospective Assessment of Rhinovirus Symptoms and Species Recurrence in Children With and Without an Acute Wheezing Exacerbation.

To assess if the difference in species-specific immune response to RV-C correlates with a higher frequency of reinfection, shorter time to reinfection, or different symptom severity than infections with RV-A or RV-B. Forty-three patients were enrolled of which 34 were successfully tracked longitudinally over 3 months, with nasal swabs and symptom questionnaires provided every 2 weeks to identify rhinovirus (RV) strains and the concurrent symptomatology. No difference was found in the time to reinfection with an RV species between RV-C and RV-A or RV-B (p = 0.866). There was a trend toward more rapid reinfection with the same species in RV-C than RV-A (55.1 days vs. 67.9 days), but this failed to reach statistical significance (p = 0.105). RV infections were generally associated with only minor symptoms, with rhinorrhea being the only significantly associated symptom (p = 0.01). RV-C was shown to have higher levels of lethargy and wheeze than other RV species. Time to reinfection with subsequent RV is not influenced by the species of the preceding RV.

Virus/Allergen Interaction in Asthma Exacerbation.

Allergy and viral respiratory infections have long been recognized as two of the most important risk factors for exacerbations of asthma. These observations have raised questions regarding potential interactions between these two important risk factors. For example, does allergy diminish the antiviral response, thereby promoting exacerbations of asthma? Alternately, do viral respiratory infections potentiate ongoing allergic inflammation in the airway? The answers to these questions are likely to have implications regarding the prevention and treatment of exacerbations of asthma. This article reviews that clinical evidence linking viral infections and allergy to exacerbations of asthma, reviews potential interactions between these two risk factors, and discusses possible application of new insights in virus/allergen interactions to the prevention and treatment of exacerbations of asthma.

Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life.

RATIONALE: Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood. OBJECTIVE: To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing. METHODS: A total of 285 children at high risk for allergic disease and asthma were followed prospectively from birth. The timing and etiology of viral respiratory wheezing illnesses were determined, and aeroallergen sensitization was assessed annually for the first 6 years of life. The relationships between these events were assessed using a longitudinal multistate Markov model. MEASUREMENTS AND MAIN RESULTS: Children who were sensitized to aeroallergens had greater risk of developing viral wheeze than nonsensitized children (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.2-3.1). Allergic sensitization led to an increased risk of wheezing illnesses caused by human rhinovirus (HRV) but not respiratory syncytial virus. The absolute risk of sensitized children developing viral wheeze was greatest at 1 year of age; however, the relative risk was consistently increased at every age assessed. In contrast, viral wheeze did not lead to increased risk of subsequent allergic sensitization (HR, 0.76; 95% CI, 0.50-1.1). CONCLUSIONS: Prospective, repeated characterization of a birth cohort demonstrated that allergic sensitization precedes HRV wheezing and that the converse is not true. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to more severe HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway. Therefore, therapeutics aimed at preventing allergic sensitization may modify virus-induced wheezing and the development of asthma.