scholarly journals Inactivation of Zika Virus by Photoactive Iodonaphthyl Azide Preserves Immunogenic Potential of the Virus

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 188
Author(s):  
Austin ◽  
Galasso ◽  
Nickens ◽  
Knollmann-Ritschel ◽  
Sharma

Zika virus’s (ZIKV) emergence as a pathogen of significant public health importance has accelerated efforts to develop a ZIKV vaccine. To date, the need for an effective ZIKV vaccine is unmet. In this study, we report inactivation of ZIKV using a hydrophobic photoactive compound: 1, 5 iodonaphthyl azide (INA). 50 and 100 µM of INA completely inactivated ZIKV (INA-ZIKV). Western blot and ELISA analysis show some loss of the binding capacity of INA-iZIKV to anti-ZIKV monoclonal antibodies; however, immunization of mice with INA-iZIKV demonstrated seroconversion and ZIKV-neutralizing antibody response. RNA isolated from INA-iZIKV did not induce productive infection in Vero cells, suggesting inactivation of ZIKV RNA. These results suggest that in the absence of an approved ZIKV vaccine, INA-iZIKV can be pursued as a viable ZIKV vaccine candidate.

2021 ◽  
Author(s):  
Daniele Focosi ◽  
Fabrizio Maggi ◽  
Massimo Franchini ◽  
Scott McConnell ◽  
Arturo Casadevall

Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former is mainly associated with specific single amino acid mutations at residues within the receptor-binding domain (e.g., E484K/Q, Q493R, and S494P), the few cases of immune evasion after CCP were associated with recurrent deletions within the N-terminal domain of Spike protein (e.g, delHV69-70, delLGVY141-144 and delAL243-244). Continuous genomic monitoring of non-responders is needed to better understand immune escape frequencies and fitness of emerging variants.


2004 ◽  
Vol 70 (12) ◽  
pp. 7574-7577 ◽  
Author(s):  
Ling Zhou ◽  
Ronald Fayer ◽  
James M. Trout ◽  
Una M. Ryan ◽  
Frank W. Schaefer ◽  
...  

ABSTRACT Of 471 specimens examined from foxes, raccoons, muskrats, otters, and beavers living in wetlands adjacent to the Chesapeake Bay, 36 were positive for five types of Cryptosporidium, including the C. canis dog and fox genotypes, Cryptosporidium muskrat genotypes I and II, and Cryptosporidium skunk genotype. Thus, fur-bearing mammals in watersheds excreted host-adapted Cryptosporidium oocysts that are not known to be of significant public health importance.


Author(s):  
Nanda Kishore Routhu ◽  
Sailaja Gangadhara ◽  
Narayanaiah Cheedarla ◽  
Ayalnesh Shiferaw ◽  
Sheikh Abdul Rahman ◽  
...  

AbstractThere is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.


Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1346
Author(s):  
Jennifer K. DeMarco ◽  
Joshua M. Royal ◽  
William E. Severson ◽  
Jon D. Gabbard ◽  
Steve Hume ◽  
...  

We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.


2020 ◽  
Vol 13 (11) ◽  
pp. 503
Author(s):  
AhmadAli Hanafi-Bojd ◽  
Javad Rafinejad ◽  
Mehran Shahi ◽  
Shahrokh Navidpour ◽  
Elham Jahanifard

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1142
Author(s):  
Danielle Porier ◽  
Sarah Wilson ◽  
Dawn Auguste ◽  
Andrew Leber ◽  
Sheryl Coutermarsh-Ott ◽  
...  

Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation in vitro and showed no hematological, histological or pathogenic effects in vivo. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4+ and CD8+ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Md. Ashfikur Rahman ◽  
Henry Ratul Halder ◽  
Uday Narayan Yadav ◽  
Sabuj Kanti Mistry

AbstractMost studies either followed Joint National Committee 7 (JNC 7) or World Health Organization-International Society of Hypertension (WHO-ISH) guidelines to ascertain the prevalence of hypertension among Bangladeshi adults. The American College of Cardiology/American Heart Association (ACC/AHA) revised the definition of hypertension in 2017, which has significant public health importance. In Bangladesh, the new guideline has resulted changes in prevalence and risk factors for hypertension compared to the JNC7 guideline. This study used data from the most recent round (2017–2018) of the Bangladesh Demographic and Health Survey (BDHS). According to the 2017 ACC/AHA guideline, the participants were categorized as hypertensive if they had blood pressure (BP) ≥ 130/80 mmHg, but it was ≥ 140/90 mmHg in JNC 7 guideline. A total of 11,959 participants were involved in the analysis. The median (IQR) age of the respondents was 34.0 (18.0–95.0) years. The prevalence of hypertension was 24.0% according to the JNC 7 guideline, which was 50.5% according to the 2017 ACC/AHA guideline. Participants who were overweight and obese, aged, member of affluent households, Rangpur and Rajshahi division inhabitants had significantly higher odds of being hypertensive according to both guidelines. The new guideline suggests that half of the adult population in Bangladesh is hypertensive when measured according to the new guideline, urging the policymakers and public health practitioners to take immediate action to address the already established modifiable risk factors.


Author(s):  
P.J. Klasse ◽  
John P. Moore

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID- 19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients and with monoclonal antibodies against the viral S-protein. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
PJ Klasse ◽  
John P Moore

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID-19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients, monoclonal antibodies against the viral S-protein, and soluble forms of the receptor for the virus, angiotensin converting enzyme 2. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.


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