scholarly journals Combination attenuation offers strategy for live-attenuated coronavirus vaccines

2018 ◽  
Author(s):  
Vineet D. Menachery ◽  
Lisa E. Gralinski ◽  
Hugh D. Mitchell ◽  
Kenneth H. Dinnon ◽  
Sarah R. Leist ◽  
...  
Keyword(s):  
Public Health ◽  
Vulnerable Populations ◽  
Global Public Health ◽  
Vaccine Strategy ◽  
Live Attenuated Vaccine ◽  
Virus Challenge ◽  
Heterologous Challenge ◽  
Heterologous Virus ◽  
New Strategies ◽  
Zoonotic Strains

AbstractWith an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live-attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2’O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the SARS-CoV mouse model, a NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2’O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2’O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live-attenuated coronavirus vaccines.SignificanceEmergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations like the aged and immune-compromised. This study illustrates that despite success in young models, the NSP16 mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the NSP16 mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for NSP16 attenuation as a major component of future live-attenuated coronavirus vaccines.

scholarly journals Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Vineet D. Menachery ◽  
Lisa E. Gralinski ◽  
Hugh D. Mitchell ◽  
Kenneth H. Dinnon ◽  
Sarah R. Leist ◽  
...  
Keyword(s):  
Public Health ◽  
Vulnerable Populations ◽  
Global Public Health ◽  
Vaccine Strategy ◽  
Live Attenuated Vaccine ◽  
Virus Challenge ◽  
Heterologous Challenge ◽  
Heterologous Virus ◽  
New Strategies ◽  
Zoonotic Strains

ABSTRACT With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2′O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2′O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2′O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated coronavirus vaccines. IMPORTANCE Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2′O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2′O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2′O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.

scholarly journals CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge

2021 ◽  
Author(s):  
Chia-En Lien ◽  
Yi-Jiun Lin ◽  
Tsun-Yung Kuo ◽  
John D Campbell ◽  
Paula Traquina ◽  
...  
Keyword(s):  
Public Health ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Clinical Development ◽  
Spike Protein ◽  
Lung Pathology ◽  
Global Public Health ◽  
Control Groups ◽  
Virus Challenge ◽  
Igg Level

The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 μg or 5 μg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

scholarly journals A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection

2018 ◽  
Vol 31 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Takuya Yamamoto ◽  
Yuji Masuta ◽  
Masatoshi Momota ◽  
Masaru Kanekiyo ◽  
Tomohiro Kanuma ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Cd8 T Cell ◽  
Influenza Vaccines ◽  
Global Public Health ◽  
Virus Challenge ◽  
Tlr9 Agonist ◽  
Heterologous Virus

Abstract The development of a universal influenza vaccine that can provide a robust and long-lasting protection against a broader range of influenza virus strains is a global public health priority. One approach to improve vaccine efficacy is to use an adjuvant to boost immune responses to the target antigens; nevertheless, the role of adjuvants in the context of influenza vaccines is not fully understood. We have previously developed the K3-schizophyllan (SPG) adjuvant, which is composed of nanoparticulated oligodeoxynucleotides K3, a TLR9 agonist, with SPG, a non-agonistic β-glucan ligand of Dectin-1. In this study, K3-SPG given with conventional influenza hemagglutinin (HA) split vaccine (K3-SPG HA) conferred protection against antigenically mismatched heterologous virus challenge. While K3-SPG HA elicited robust cross-reactive HA-specific IgG2c and CD8 T-cell responses, CD8 T-cell depletion had no impact on this cross-protection. In contrast, K3-SPG HA was not able to confer protection against heterologous virus challenge in FcRγ-deficient mice. Our results indicated that FcγR-mediated antibody responses induced by the HA antigen and K3-SPG adjuvant were important for potent protection against antigenically mismatched influenza virus infection. Thus, we demonstrated that the K3-SPG-adjuvanted vaccine strategy broadens protective immunity against influenza and provides a basis for the development of next-generation influenza vaccines.

scholarly journals Precision Health in Disaster Medicine and Global Public Health

2018 ◽  
Vol 33 (6) ◽  
pp. 565-566 ◽  
Author(s):  
Ronak B. Patel
Keyword(s):  
Public Health ◽  
Global Health ◽  
Precision Medicine ◽  
Vulnerable Populations ◽  
Disaster Medicine ◽  
Limited Resources ◽  
Global Public Health ◽  
Publication Type ◽  
New Approaches ◽  
Precision Health

AbstractCurrent debates about precision medicine take different perspectives on its relevance and value in global health. The term has not yet been applied to disaster medicine or humanitarian health, but it may hold significant value. An interpretation of the term for global public health and disaster medicine is presented here for application to vulnerable populations. Embracing the term may drive more efficient use and targeting of limited resources while encouraging innovation and adopting the new approaches advocated in current humanitarian discourse.PatelRB.Precision health in disaster medicine and global public health.Prehosp Disaster Med.2018;33(6):565–566.

scholarly journals CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chia-En Lien ◽  
Yi-Jiun Lin ◽  
Charles Chen ◽  
Wei-Cheng Lian ◽  
Tsun-Yung Kuo ◽  
...  
Keyword(s):  
Public Health ◽  
Neutralizing Antibodies ◽  
Rapid Development ◽  
Clinical Development ◽  
Spike Protein ◽  
Lung Pathology ◽  
Global Public Health ◽  
Control Groups ◽  
Virus Challenge ◽  
Igg Level

AbstractThe COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

Life Lessons of the Pandemic ”Covid - 19”

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 469-471 ◽  
Author(s):  
Bhagyashri Vijay Chaudhari ◽  
Priya P. Chawle
Keyword(s):  
Public Health ◽  
Review Article ◽  
Public Health Emergency ◽  
The Novel ◽  
Global Public Health ◽  
Strange Situation ◽  
Republic Of China ◽  
Lifetime History ◽  
The People ◽  
Life Lessons

“A lesson learned the hard way is a lesson learned for a lifetime.” Every bad situation hurts; however, it sure does teach us something a lesson. In the same manner of a new lesson for Human lifetime, history is observing 'The Novel COVID-19 ’, a very horrible and strange situation created due to fighting with a microscopic enemy. WHO on 11 February 2020 has announced a name for new disease as - 19 and has declared as a global public health emergency and subsequently as pandemic because of its widespread. This began as an outbreak in December 2019, with its in Wuhan, the People Republic of China has emerged as a public health emergency of international concern. is the group of a virus with non-segmented, single-stranded and positive RNA genome. This bad situation of pandemic creates new scenes in the life of people in a different manner, which will be going to be life lessons for them. Such lessons should be kept in mind for the safety of living beings and many more things. In this narrative review article, reference was taken from a different article published in various databases which include the view of different authors and writers on the "Lessons to be from Corona".

Can Mandated BCG Vaccine Promote herd Immunity against Novel Coronavirus? A Potential Solution at Hand to Tackle Covid-19 Pandemic

2020 ◽  
Vol 16 (1) ◽  
pp. 6-11
Author(s):  
Ashok Arasu ◽  
Pavithra Balakrishnan ◽  
Thirunavukkarasu Velusamy ◽  
Thiagarajan Ramesh
Keyword(s):  
Protective Factor ◽  
Herd Immunity ◽  
Bcg Vaccine ◽  
Intestinal Cells ◽  
Global Public Health ◽  
Wuhan City ◽  
Live Attenuated Vaccine ◽  
Angiotensin Converting Enzyme 2 ◽  
Lung Epithelial ◽  
Novel Coronavirus

The 2019 novel coronavirus (2019-nCoV) infection is an emerging pandemic that poses a severe threat to global public health. This pandemic started from the Wuhan City of Hubei Province in China, and is speculated to have originated from bats and spread among humans with an unknown intermediate transmitter. The virus binds to angiotensin-converting enzyme 2 (ACE2), which is abundantly expressed on various human cells, including lung epithelial and intestinal cells, thereby entering into these cells and causing infection. It is transmitted to other humans through airborne droplets from infected patients. Presently there are no specific treatments or vaccines that are available to curtail the spread of this disease. There are few indirect reports that explain the potential importance of the mandated BCG vaccine as a protective factor against COVID-19. There is a speculation that a live attenuated vaccine (BCG vaccine) can be beneficial against COVID-19 to develop the initial immune response, and can also spread in the community, thereby boosting herd immunity to fight against COVID-19. This review summarizes the conclusions of various reports on the BCG vaccine, and is an attempt to establish BCG-vaccination mediated herd immunity as an effective instant intermediate approach in curbing COVID-19 spread in highly populous countries.

Application of Inherent Risk of Contagion (IRC) framework & modelling to aid local Covid-19 response & mitigation: Viewpoint (Preprint)

2020 ◽  
Author(s):  
Helmi Zakariah ◽  
Fadzilah bt Kamaluddin ◽  
Choo-Yee Ting ◽  
Hui-Jia Yee ◽  
Shereen Allaham ◽  
...  
Keyword(s):  
Public Health ◽  
Public Health Problem ◽  
Analytical Framework ◽  
Vulnerable Population ◽  
Contact Tracing ◽  
Global Public Health ◽  
Inherent Risk ◽  
Transmission Area ◽  
Current Outbreak ◽  
Novel Coronavirus

UNSTRUCTURED The current outbreak of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus named SARS-CoV-2 has been a major global public health problem threatening many countries and territories. Mathematical modelling is one of the non-pharmaceutical public health measures that plays a crucial role for mitigating the risk and impact of the pandemic. A group of researchers and epidemiologists have developed a machine learning-powered inherent risk of contagion (IRC) analytical framework to georeference the COVID-19 with an operational platform to plan response & execute mitigation activities. This framework dataset provides a coherent picture to track and predict the COVID-19 epidemic post lockdown by piecing together preliminary data on publicly available health statistic metrics alongside the area of reported cases, drivers, vulnerable population, and number of premises that are suspected to become a transmission area between drivers and vulnerable population. The main aim of this new analytical framework is to measure the IRC and provide georeferenced data to protect the health system, aid contact tracing, and prioritise the vulnerable.

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