Novel Inactivated Subtype B Avian Metapneumovirus Vaccine Induced Humoral and Cellular Immune Responses

Avian metapneumovirus (aMPV), a highly contagious agent, is widespread and causes acute upper respiratory tract disease in chickens and turkeys. However, currently, there is no vaccine licensed in China. Herein, we describe the development of an inactivated aMPV/B vaccine using the aMPV/B strain LN16. Combined with a novel adjuvant containing immune-stimulating complexes (ISCOMs), the novel vaccine could induce high virus-specific and VN antibodies. In addition, it activated B and T lymphocytes and promoted the expression of IL-4 and IFN-γ. Importantly, boosting vaccination with the inactivated aMPV/B vaccine could provide 100% protection against aMPV/B infection with reduced virus shedding and turbinate inflammation. The protection efficacy could last for at least 6 months. This study yielded a novel inactivated aMPV/B vaccine that could serve as the first vaccine candidate in China, thus contributing to the control of aMPV/B and promoting the development of the poultry industry.

Download Full-text

Complete Genome Sequence of an Avian Metapneumovirus Subtype B Strain from Hungary

Microbiology Resource Announcements ◽

10.1128/mra.00177-20 ◽

2020 ◽

Vol 9 (19) ◽

Author(s):

Iryna V. Goraichuk ◽

Darrell R. Kapczynski ◽

Bruce S. Seal ◽

David L. Suarez

Keyword(s):

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Upper Respiratory Tract ◽

Respiratory Tract Disease ◽

Avian Metapneumovirus ◽

Subtype B ◽

Upper Respiratory ◽

Tract Disease ◽

Generation Sequencing

Avian metapneumoviruses (aMPVs), which have been reported in many countries, cause acute upper respiratory tract disease in chickens and turkeys. Using next-generation sequencing, we report here the complete genome sequence of an aMPV subtype B strain that was isolated from a turkey in Hungary in 1989.

Download Full-text

Induction of Broad-Based Immunity and Protective Efficacy by Self-amplifying mRNA Vaccines Encoding Influenza Virus Hemagglutinin

Journal of Virology ◽

10.1128/jvi.01786-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 332-344 ◽

Cited By ~ 54

Author(s):

Michela Brazzoli ◽

Diletta Magini ◽

Alessandra Bonci ◽

Scilla Buccato ◽

Cinzia Giovani ◽

...

Keyword(s):

T Cells ◽

Influenza Virus ◽

Immune Responses ◽

Upper Respiratory Tract ◽

Vaccine Platform ◽

Major Health Problem ◽

Cellular Immune Responses ◽

Influenza Virus Hemagglutinin ◽

Cellular Immune ◽

The Impact

ABSTRACTSeasonal influenza is a vaccine-preventable disease that remains a major health problem worldwide, especially in immunocompromised populations. The impact of influenza disease is even greater when strains drift, and influenza pandemics can result when animal-derived influenza virus strains combine with seasonal strains. In this study, we used the SAM technology and characterized the immunogenicity and efficacy of a self-amplifying mRNA expressing influenza virus hemagglutinin (HA) antigen [SAM(HA)] formulated with a novel oil-in-water cationic nanoemulsion. We demonstrated that SAM(HA) was immunogenic in ferrets and facilitated containment of viral replication in the upper respiratory tract of influenza virus-infected animals. In mice, SAM(HA) induced potent functional neutralizing antibody and cellular immune responses, characterized by HA-specific CD4 T helper 1 and CD8 cytotoxic T cells. Furthermore, mice immunized with SAM(HA) derived from the influenza A virus A/California/7/2009 (H1N1) strain (Cal) were protected from a lethal challenge with the heterologous mouse-adapted A/PR/8/1934 (H1N1) virus strain (PR8). Sera derived from SAM(H1-Cal)-immunized animals were not cross-reactive with the PR8 virus, whereas cross-reactivity was observed for HA-specific CD4 and CD8 T cells. Finally, depletion of T cells demonstrated that T-cell responses were essential in mediating heterologous protection. If the SAM vaccine platform proves safe, well tolerated, and effective in humans, the fully synthetic SAM vaccine technology could provide a rapid response platform to control pandemic influenza.IMPORTANCEIn this study, we describe protective immune responses in mice and ferrets after vaccination with a novel HA-based influenza vaccine. This novel type of vaccine elicits both humoral and cellular immune responses. Although vaccine-specific antibodies are the key players in mediating protection from homologous influenza virus infections, vaccine-specific T cells contribute to the control of heterologous infections. The rapid production capacity and the synthetic origin of the vaccine antigen make the SAM platform particularly exploitable in case of influenza pandemic.

Download Full-text

Humoral and cellular immunity and the safety of COVID-19 vaccines: a summary of data published by 21 May 2021

International Immunology ◽

10.1093/intimm/dxab061 ◽

2021 ◽

Vol 33 (10) ◽

pp. 529-540

Author(s):

Kun Xu ◽

Lianpan Dai ◽

George F Gao

Keyword(s):

Immune Responses ◽

Viral Genome ◽

Vaccine Development ◽

Published Data ◽

Humoral And Cellular Immunity ◽

Cellular Immune Responses ◽

Rapid Responses ◽

Study Results ◽

Protection Efficacy ◽

Cellular Immune

Abstract Coronavirus disease 2019 (COVID-19) has caused millions of deaths, and serious consequences to public health, economies and societies. Rapid responses in vaccine development have taken place since the isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the release of the viral genome sequence. By 21 May 2021, 101 vaccines were under clinical trials, and published data were available for 18 of them. Clinical study results from some vaccines indicated good immunogenicity and acceptable reactogenicity. Here, we focus on these 18 vaccines that had published clinical data to dissect the induced humoral and cellular immune responses as well as their safety profiles and protection efficacy.

Download Full-text

Development of a Recombinant RBD Subunit Vaccine for SARS-CoV-2

Viruses ◽

10.3390/v13101936 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1936

Author(s):

Yi-Sheng Sun ◽

Jing-Jing Zhou ◽

Han-Ping Zhu ◽

Fang Xu ◽

Wen-Bin Zhao ◽

...

Keyword(s):

Subunit Vaccine ◽

Neutralizing Antibody ◽

Human Society ◽

The Novel ◽

Subunit Vaccines ◽

Cellular Immune Responses ◽

Human Igg1 ◽

Ifn Γ ◽

Novel Coronavirus ◽

Cellular Immune

The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future. The receptor binding domain (RBD), located at the S protein of SARS-CoV-2, contains most of the neutralizing epitopes. However, the immunogenicity of RBD monomers is not strong enough. In this study, we fused the RBD-monomer with a modified Fc fragment of human IgG1 to form an RBD-Fc fusion protein. The recombinant vaccine candidate based on the RBD-Fc protein could induce high levels of IgG and neutralizing antibody in mice, and these could last for at least three months. The secretion of IFN-γ, IL-2 and IL-10 in the RBD-stimulated splenocytes of immunized mice also increased significantly. Our results first showed that the RBD-Fc vaccine could induce both humoral and cellular immune responses and might be an optional strategy to control COVID-19.

Download Full-text

Virological assessment of hospitalized cases of coronavirus disease 2019

10.1101/2020.03.05.20030502 ◽

2020 ◽

Cited By ~ 100

Author(s):

Roman Wölfel ◽

Victor M. Corman ◽

Wolfgang Guggemos ◽

Michael Seilmaier ◽

Sabine Zange ◽

...

Keyword(s):

Respiratory Tract ◽

Virus Replication ◽

Acute Respiratory Tract Infection ◽

Rapid Decline ◽

Upper Respiratory Tract ◽

Virus Shedding ◽

Active Virus ◽

Virus Rna ◽

Upper Respiratory ◽

High Virus

Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 20191,2. Initial outbreaks in China involved 13.8% cases with severe-, and 6.1% with critical courses3. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung2,4. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity but also aided the control of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting a potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on body site - specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 × 108 RNA copies per throat swab, day 4). Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat- and lung samples of one same patient. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 6-12 days, but was not followed by a rapid decline of viral loads. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts prospects of COVID-19 containment in perspective.

Download Full-text

Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B

10.1101/2021.05.11.443286 ◽

2021 ◽

Author(s):

Jun Liu ◽

Patrick Budylowski ◽

Reuben Samson ◽

Bryan D Griffin ◽

Giorgi Babuadze ◽

...

Keyword(s):

Immune Responses ◽

Phase 1 ◽

Neutralizing Antibody ◽

Upper Respiratory Tract ◽

Preclinical Development ◽

Preclinical Evaluation ◽

Cellular Immune Responses ◽

Upper Respiratory ◽

Cellular Immune ◽

Health Canada

Safe and effective vaccines are needed to end the COVID-19 pandemic caused by SARS-CoV-2. Here we report the preclinical development of a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern (VOCs), including the B.1.1.7, B.1.351 and P.1 lineages. No adverse effects were induced by PTX-COVID19-B in both mice and hamsters. These preclinical results indicate that PTX-COVID19-B is safe and effective. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 1 clinical trial ongoing (ClinicalTrials.gov number: NCT04765436).

Download Full-text