Prospects for mucosal vaccine: shutting the door on SARS-CoV-2

Mudgal, Rajat; Nehul, Sanketkumar; Tomar, Shailly

doi:10.1080/21645515.2020.1805992

Cited by 89 publications

(80 citation statements)

References 133 publications

(153 reference statements)

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“…Human ACE2 protein contains 805 amino acids and has two functional domains, i.e., N-terminal peptidase M2 domain and C-terminal collectrin domain, which have been reported to contain the residues involved in the spike protein binding [ 27 , 33 ]. This binding site is considered to be an entry door for the virus and several vaccine approaches are based on shutting this entry door in the host cells to combat this unprecedented pandemic [ 34 ]. Ensembl Genome Browser and gnomAD exhibited 345 and 242 natural ACE2 coding variants, respectively.…”

Section: Resultsmentioning

confidence: 99%

Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism

et al. 2021

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 × 10−3 to 5.47 × 10−6 for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.

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Section: Resultsmentioning

confidence: 99%

Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism

et al. 2021

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“…Indeed, systemic vaccines such as mRNA and adenovirus vaccines provided only limited protection against input viral clearance and resulted in persistent viral presence in nasal swabs [ 36 , 38 , 43 ]. Prospectively, mucosal vaccines were proposed to be better at clearing the virus in the airways, and thus preventing virus transmission [ 50 , 75 , 76 ]. A mucosal vaccine which is in development in our lab showed more effective clearance of nasal input virus than a systemic vaccine (unpublished data).…”

Section: Mucosal Immunity Protects Viral Transmission At the Frontmentioning

confidence: 99%

Potential SARS-CoV-2 Immune Correlates of Protection in Infection and Vaccine Immunization

2021

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Both SARS-CoV-2 infections and vaccines induce robust immune responses. Current data suggested that high neutralizing antibody titers with sustained Th1 responses might correlate with protection against viral transmission and disease development and severity. In addition, genetic and innate immune factors, including higher levels of type I interferons, as well as the induction of trained immunity and local mucosal immunity also contribute to lower risk of infection and amelioration of disease severity. The identification of immune correlates of protection will facilitate the development of effective vaccines and therapeutics strategies.

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“…As mention previously, mucosal surfaces serve as the primary portal of entry for most pathogens. Hence, mucosal vaccination provides a safe and efficient mechanism to induce systemic and mucosal immunity against pathogens ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Novel Mucosal Administered Subunit Vaccine on Colostrum IgA and Serum IgG in Sows and Control of Enterotoxigenic Escherichia coli in Neonatal and Weanling Piglets: Proof of Concept

Jabif¹,

Gumina²,

Hall³

et al. 2021

Front. Vet. Sci.

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The purpose of the present study was to evaluate the ability of a novel experimental subunit vaccine (ESV), induce colostrum IgA and serum IgG in sows, and to control enterotoxigenic Escherichia coli (ETEC) disease in neonatal and weanling piglets. The vaccine was tested in three experiments. Experiment 1 consisted of two independent trials. In each trial, 20 pregnant sows/groups were vaccinated intramuscularly (IM) with a commercial E. coli vaccine or intranasally with ESV at weeks 11 and 13 of pregnancy. Blood and serum samples were obtained within 12 h post-partum. In Experiment 1, intranasal vaccination with ESV significantly increased the sample-to-positive (S/P) ratio of secretory IgA in the colostrum of sows (P < 0.01, trial 1; P < 0.05, trial 2) compared to the IM vaccine. In Experiment 2, twenty-five 3-day old piglets were randomly allocated into two groups, control (n = 13) or ESV (n = 12) and were oral gavaged with the respective treatments on days 3 and 14 of life. On days 17–19, all piglets were challenged using a mixed ETEC culture via oral gavage. Within 72 h, all control group animals developed disease consistent with colibacillosis. Conversely, the ESV treated group remained disease free over the 7-day observation period and had significant increases in body weight gain compared to the control group piglets. In Experiment 3, thirty 28-day old piglets were randomly allocated, control (n = 15) or ESV (n = 15), and on days 33 and 43 of life, piglets were either given by oral gavage 2.0 mL saline (control group) or 2.0 mL ESV. At days 46 and 47 of life, all pigs were challenged with a mixed culture of ETEC and observed for clinical signs of disease. Results of Experiment 3 were similar to those observed in Experiment 2. This study indicates the ESV can induce better levels of colostrum secretory IgA in pregnant sows than IM vaccination, which may be protective to neonatal piglets. Further, the vaccine can protect piglets as early as 3 days of age from an ETEC infection. Importantly, the data suggest a single vaccine could be used across the farrowing, suckling, and weaning program to protect against pathogenic E. coli.

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Prospects for mucosal vaccine: shutting the door on SARS-CoV-2

Cited by 89 publications

References 133 publications

Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism

Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism

Potential SARS-CoV-2 Immune Correlates of Protection in Infection and Vaccine Immunization

Evaluation of a Novel Mucosal Administered Subunit Vaccine on Colostrum IgA and Serum IgG in Sows and Control of Enterotoxigenic Escherichia coli in Neonatal and Weanling Piglets: Proof of Concept

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