scholarly journals Evaluation of a Single-Dose Nucleoside-Modified Messenger RNA Vaccine Encoding Hendra Virus-Soluble Glycoprotein Against Lethal Nipah virus Challenge in Syrian Hamsters

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S493-S498 ◽  
Author(s):  
Michael K Lo ◽  
Jessica R Spengler ◽  
Stephen R Welch ◽  
Jessica R Harmon ◽  
JoAnn D Coleman-McCray ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
Messenger Rna ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Highly Pathogenic ◽  
Syrian Hamsters ◽  
Virus Challenge ◽  
Pathogenic Viruses ◽  
Rna Vaccine

Abstract In the absence of approved vaccines and therapeutics for use in humans, Nipah virus (NiV) continues to cause fatal outbreaks of encephalitis and respiratory disease in Bangladesh and India on a near-annual basis. We determined that a single dose of a lipid nanoparticle nucleoside-modified messenger RNA vaccine encoding the soluble Hendra virus glycoprotein protected up to 70% of Syrian hamsters from lethal NiV challenge, despite animals having suboptimally primed immune responses before challenge. These data provide a foundation from which to optimize future messenger RNA vaccination studies against NiV and other highly pathogenic viruses.

scholarly journals Coadministration of Cidofovir and Smallpox Vaccine Reduced Vaccination Side Effects but Interfered with Vaccine-Elicited Immune Responses and Immunity to Monkeypox

2008 ◽  
Vol 83 (2) ◽  
pp. 1115-1125 ◽  
Author(s):  
Huiyong Wei ◽  
Dan Huang ◽  
Jeff Fortman ◽  
Richard Wang ◽  
Linyun Shao ◽  
...  
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Immune Responses ◽  
Antiviral Agent ◽  
Smallpox Vaccine ◽  
Effector Cells ◽  
Virus Challenge ◽  
T Effector Cells ◽  
Viral Loads ◽  
Induced Immunity

ABSTRACT While the smallpox vaccine, Dryvax or Dryvax-derived ACAM2000, holds potential for public immunization against the spread of smallpox by bioterror, there is serious concern about Dryvax-mediated side effects. Here, we report that a single-dose vaccination regimen comprised of Dryvax and an antiviral agent, cidofovir, could reduce vaccinia viral loads after vaccination and significantly control Dryvax vaccination side effects. However, coadministration of cidofovir and Dryvax also reduced vaccine-elicited immune responses of antibody and T effector cells despite the fact that the reduced priming could be boosted as a recall response after monkeypox virus challenge. Evaluations of four different aspects of vaccine efficacy showed that coadministration of cidofovir and Dryvax compromised the Dryvax-induced immunity against monkeypox, although the covaccinated monkeys exhibited measurable protection against monkeypox compared to that of naïve controls. Thus, the single-dose coadministration of cidofovir and Dryvax effectively controlled vaccination side effects but significantly compromised vaccine-elicited immune responses and vaccine-induced immunity to monkeypox.

scholarly journals Heparan Sulfate-Dependent Enhancement of Henipavirus Infection

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Cyrille Mathieu ◽  
Kévin P. Dhondt ◽  
Marie Châlons ◽  
Stéphane Mély ◽  
Hervé Raoul ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Anticoagulant Activity ◽  
Antiviral Treatment ◽  
Mammalian Species ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Host Cells ◽  
Emerging Infections ◽  
Highly Pathogenic

ABSTRACTNipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genusHenipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirustrans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediatedtrans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cellsin vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections.IMPORTANCETheHenipavirusgenus includes two closely related, highly pathogenic paramyxoviruses, Nipah virus and Hendra virus, which cause elevated morbidity and mortality in animals and humans. Pathogenesis of both Nipah virus and Hendra virus infection is poorly understood, and efficient antiviral treatment is still missing. Here, we identified heparan sulfate as a novel attachment receptor used by both viruses to bind host cells. We demonstrate that heparin was able to inhibit the interaction of the viruses with heparan sulfate and to block cell-mediatedtrans-infection of henipaviruses. Moreover, heparin also bound to the viral entry receptor and thereby restricted infection of permissive cellsin vitro. Consequently, heparin treatment improved survival of Nipah virus-infected hamsters. These results uncover an important role of heparan sulfate in henipavirus infection and open novel perspectives for the development of heparan sulfate-targeting therapeutic approaches for these emerging infections.

scholarly journals A Hendra Virus G Glycoprotein Subunit Vaccine Protects African Green Monkeys from Nipah Virus Challenge

2012 ◽  
Vol 4 (146) ◽  
pp. 146ra107-146ra107 ◽  
Author(s):  
K. N. Bossart ◽  
B. Rockx ◽  
F. Feldmann ◽  
D. Brining ◽  
D. Scott ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Virus Challenge ◽  
Green Monkeys

scholarly journals A single dose investigational subunit vaccine for human use against Nipah virus and Hendra virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Thomas W. Geisbert ◽  
Kathryn Bobb ◽  
Viktoriya Borisevich ◽  
Joan B. Geisbert ◽  
Krystle N. Agans ◽  
...  
Keyword(s):  
Single Dose ◽  
Subunit Vaccine ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Vaccine Formulation ◽  
Protein Subunit ◽  
Primate Model ◽  
Virus Attachment ◽  
A Subunit ◽  
Human Vaccine

AbstractNipah and Hendra viruses are highly pathogenic bat-borne paramyxoviruses recently included in the WHO Blueprint priority diseases list. A fully registered horse anti-Hendra virus subunit vaccine has been in use in Australia since 2012. Based on the same immunogen, the Hendra virus attachment glycoprotein ectodomain, a subunit vaccine formulation for use in people is now in a Phase I clinical trial. We report that a single dose vaccination regimen of this human vaccine formulation protects against otherwise lethal challenges of either Hendra or Nipah virus in a nonhuman primate model. The protection against the Nipah Bangladesh strain begins as soon as 7 days post immunization with low dose of 0.1 mg protein subunit. Our data suggest this human vaccine could be utilized as efficient emergency vaccine to disrupt potential spreading of Nipah disease in an outbreak setting.

scholarly journals Nipah virus in India: past, present and future

2018 ◽  
Vol 5 (9) ◽  
pp. 3653 ◽  
Author(s):  
Prarthana M. S.
Keyword(s):  
Environmental Changes ◽  
Nipah Virus ◽  
Case Fatality ◽  
Hendra Virus ◽  
High Morbidity ◽  
Surveillance Strategy ◽  
Rapid Urbanization ◽  
Highly Pathogenic ◽  
Effective Prevention ◽  
North East

Nipah virus (NiV) is one of the emerging highly pathogenic virus. Like Ebola and Zika viruses, NiV too is threatening the integrity of the mankind. The family Paramyxoviruses has been traditionally associated with a group of viruses with narrow host range and typically causes outbreaks with low mortality rates. But with the emergence of highly pathogenic Hendra virus and closely related NiV, they have evolved as a cause of fatal encephalitis across broad range of vertebrate species including humans. The natural reservoir of NiV is Pteropus bat, which is apparently distributed all over the South East Asia. The bat population from North East to North West states in India have NiV antibodies which mean there is active NiV infection among Indian bats. As NiV is associated with high morbidity and mortality they pose a risk from natural outbreaks, laboratory accidents or deliberate misuse. The development of effective prevention and treatment strategies is very crucial. Preparedness, surveillance, constant vigil needs to be carried out continuously in the country. The present outbreak in India after nearly eleven years with a high case fatality rate indicate that there is a total lack of health care systems preparedness and surveillance strategy. The anthropogenic and environmental changes occurring due to rapid urbanization and massive deforestation has made India now even more vulnerable for such recurrent outbreaks. This review highlights the changing trend of the NiV outbreaks in the past and the current outbreak in India.

scholarly journals A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients

2021 ◽  
Author(s):  
Charles Hugo MARQUETTE ◽  
Emanuela MARTINUZZI ◽  
Jonathan BENZAQUEN ◽  
Olivier GUERIN ◽  
Sylvie LEROY ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
Vaccine Dose ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Virus Shedding ◽  
Booster Injection ◽  
Specific Igg ◽  
Mucosal Immune Responses ◽  
Rna Vaccine

Background: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine. Methods: Twenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism. Results: In COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine doses Conclusion: This study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.

scholarly journals Complete protection by a single dose skin patch delivered SARS-CoV-2 spike vaccine

2021 ◽  
Author(s):  
Christopher L.D. McMillan ◽  
Jovin J.Y. Choo ◽  
Adi Idris ◽  
Aroon Supramaniam ◽  
Naphak Modhiran ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
Subunit Vaccine ◽  
High Density ◽  
Complete Protection ◽  
Virus Challenge ◽  
Skin Patch

SARS-CoV-2 has infected over 160 million people and resulted in more than 3.3 million deaths, and we still face many challenges in the rollout of vaccines. Here, we use the high-density microarray patch to deliver a SARS-CoV-2 spike subunit vaccine directly to the skin. We show the vaccine, dry-coated on the patch is thermostable, and delivery of spike via HD-MAP induced greater cellular and antibody immune responses, with serum able to potently neutralize clinically relevant isolates including those from the B.1.1.7 and B.1.351 lineages. Finally, a single dose of HD-MAP-delivered spike provided complete protection from a lethal virus challenge, demonstrating that HD-MAP delivery of a SARS-CoV-2 vaccine is superior to traditional needle-and-syringe vaccination and has the potential to greatly impact the ongoing COVID-19 pandemic.

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