Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

A highly potent antibody effective against SARS-CoV-2 variants of concern.

Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals

Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity

Calf health from birth to weaning. III. housing and management of calf pneumonia

Calfhood diseases have a major impact on the economic viability of cattle operations. A three part review series has been developed focusing on calf health from birth to weaning. In this paper, the last of the three part series, we review disease prevention and management with particular reference to pneumonia, focusing primarily on the pre-weaned calf. Pneumonia in recently weaned suckler calves is also considered, where the key risk factors are related to the time of weaning. Weaning of the suckler calf is often combined with additional stressors including a change in nutrition, environmental change, transport and painful husbandry procedures (castration, dehorning). The reduction of the cumulative effects of these multiple stressors around the time of weaning together with vaccination programmes (preconditioning) can reduce subsequent morbidity and mortality in the feedlot. In most studies, calves housed individually and calves housed outdoors with shelter, are associated with decreased risk of disease. Even though it poses greater management challenges, successful group housing of calves is possible. Special emphasis should be given to equal age groups and to keeping groups stable once they are formed. The management of pneumonia in calves is reliant on a sound understanding of aetiology, relevant risk factors, and of effective approaches to diagnosis and treatment. Early signs of pneumonia include increased respiratory rate and fever, followed by depression. The single most important factor determining the success of therapy in calves with pneumonia is early onset of treatment, and subsequent adequate duration of treatment. The efficacy and economical viability of vaccination against respiratory disease in calves remains unclear

Online communication predicts Belgian adolescents’ initiation of romantic and sexual activity

Online communication is associated with offline romantic and sexual activity among college students. Yet, it is unknown whether online communication is associated with the initiation of romantic and sexual activity among adolescents. This two-wave panel study investigated whether chatting, visiting dating websites, and visiting erotic contact websites predicted adolescents’ initiation of romantic and sexual activity. We analyzed two-wave panel data from 1163 Belgian adolescents who participated in the MORES Study. We investigated the longitudinal impact of online communication on the initiation of romantic relationships and sexual intercourse using logistic regression analyses. The odds ratios of initiating a romantic relationship among romantically inexperienced adolescents who frequently used chat rooms, dating websites, or erotic contact websites were two to three times larger than those of non-users. Among sexually inexperienced adolescents who frequently used chat rooms, dating websites, or erotic contact websites, the odds ratios of initiating sexual intercourse were two to five times larger than that among non-users, even after a number of other relevant factors were introduced. Conclusion: This is the first study to demonstrate that online communication predicts the initiation of offline sexual and romantic activity as early as adolescence. Practitioners and parents need to consider the role of online communication in adolescents’ developing sexuality

Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in three-week-old calves experimentally challenged with BRSV

Bovine respiratory syncytial virus (BRSV) is a widespread cause of lower respiratory tract disease in cattle. Calves less than four months of age are often involved in outbreaks of respiratory disease. We evaluated the efficacy of a single intranasal dose of a bivalent modified live vaccine containing BRSV (Rispoval (R) RS+Pi3 Intranasal, Pfizer Ltd.) in three-week-old calves with and without maternal antibodies to BRSV Two experimental challenge studies were undertaken. In the first study, the time to onset of protection following vaccination was determined in three-week-old colostrum deprived (maternal antibody negative) calves. Calves were challenged at 5, 10 or 21 days after vaccination. Onset of immunity was demonstrated within 5 days after vaccination. After challenge, clinical signs were mostly mild and differences between vaccinated calves and controls were small but the duration of coughing (indicative of upper respiratory tract disease) was significantly shorter in the vaccinates challenged 10 days after vaccination (P = 0.0059) and the duration of hyperpnoea (indicative of lower respiratory tract disease) was significantly shorter in the vaccinates challenged 5 days after vaccination (P = 0.0253). In the second study, the efficacy of the vaccine was assessed in three-week-old calves with maternal antibodies to BRSV Vaccination significantly reduced BRSV nasal shedding after challenge 9 weeks post vaccination and a strong serological booster response was observed in the vaccinated calves following challenge. In addition, clinical signs of respiratory tract disease following challenge were less severe in the vaccinates than the controls with a lower number of mortalities in the vaccinated calves. It is concluded that a single intranasal dose of the bivalent modified live vaccine containing BRSV (Rispoval (R) RS+Pi3 Intranasal, Pfizer Ltd.) provided significant protection against BRSV shedding and disease in young calves both with and without maternal antibodies to BRSV