The Stop Codon after the nsp3 Gene of Ross River Virus (RRV) Is Not Essential for Virus Replication in Three Cell Lines Tested, but RRV Replication Is Attenuated in HEK 293T Cells.

A recombinant Ross River virus (RRV) that contains the fluorescent protein mCherry fused to the non-structural protein 3 (nsP3) was constructed, which allowed real-time imaging of viral replication. RRV-mCherry contained either the natural opal stop codon after the nsP3 gene or was constructed without a stop codon. The mCherry fusion protein did not interfere with the viral life cycle and deletion of the stop codon did not change the replication capacity of RRV-mCherry.

T-bet B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms.

Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline.

Self-Amplifying RNA Vaccine Candidates: Alternative Platforms for mRNA Vaccine Development.

The present use of mRNA vaccines against COVID-19 has shown for the first time the potential of mRNA vaccines for infectious diseases. Here we will summarize the current knowledge about improved mRNA vaccines, i.e.

Chikungunya Vaccine Candidates: Current Landscape and Future Prospects.

Chikungunya virus (CHIKV) is an alphavirus that has spread globally in the last twenty years. Although mortality is rather low, infection can result in debilitating arthralgia that can persist for years. Unfortunately, no treatments or preventive vaccines are currently licensed against CHIKV infections.

Monkeypox Goes North: Ongoing Worldwide Monkeypox Infections in Humans.

In the late 1970s, global vaccination programs resulted in the eradication of smallpox. The Monkeypox virus (MPXV), which is closely related to the smallpox-inducing variola virus, was previously endemic only in Sub-Saharan Africa but is currently spreading worldwide. Only older people who have been vaccinated against smallpox are expected to be sufficiently protected against poxviruses.

A Bivalent Trans-Amplifying RNA Vaccine Candidate Induces Potent Chikungunya and Ross River Virus Specific Immune Responses.

Alphaviruses such as the human pathogenic chikungunya virus (CHIKV) and Ross River virus (RRV) can cause explosive outbreaks raising public health concerns. However, no vaccine or specific antiviral treatment is yet available. We recently established a CHIKV vaccine candidate based on trans-amplifying RNA (taRNA).

A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections.

The arthritogenic alphavirus, chikungunya virus (CHIKV), is now present in almost 100 countries worldwide. Further spread is very likely, which raises public health concerns. CHIKV infections cause fever and arthralgia, which can be debilitating and last for years.

Longitudinal Analysis of Coronavirus-Neutralizing Activity in COVID-19 Patients.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has now been continuing for more than two years. The infection causes COVID-19, a disease of the respiratory and cardiovascular system of variable severity. Here, the humoral immune response of 80 COVID-19 patients from the University Hospital Frankfurt/Main, Germany, was characterized longitudinally.

Comparative Investigation of Methods for Analysis of SARS-CoV-2-Spike-Specific Antisera.

In light of an increasing number of vaccinated and convalescent individuals, there is a major need for the development of robust methods for the quantification of neutralizing antibodies; although, a defined correlate of protection is still missing. Sera from hospitalized COVID-19 patients suffering or not suffering from acute respiratory distress syndrome (ARDS) were comparatively analyzed by plaque reduction neutralization test (PRNT) and pseudotype-based neutralization assays to quantify their neutralizing capacity. The two neutralization assays showed comparable data.

Rapid and Sensitive SERS-Based Lateral Flow Test for SARS-CoV2-Specific IgM/IgG Antibodies.

As an immune response to COVID-19 infection, patients develop SARS-CoV-2-specific IgM/IgG antibodies. Here, we compare the performance of a conventional lateral flow assay (LFA) with a surface-enhanced Raman scattering (SERS)-based LFA test for the detection of SARS-CoV-2-specific IgM/IgG in sera of COVID-19 patients. Sensitive detection of IgM might enable early serological diagnosis of acute infections.

Development of a Sensitive Detection Method for Alphaviruses and Its Use as a Virus Neutralization Assay.

Alphaviruses have a single-stranded, positive-sense RNA genome that contains two open reading frames encoding either the non-structural or the structural genes. Upon infection, the genomic RNA is translated into the non-structural proteins (nsPs). NsPs are required for viral RNA replication and transcription driven from the subgenomic promoter (sgP).

The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists.

Comparison of potency assays to assess SARS-CoV-2 neutralizing antibody capacity in COVID-19 convalescent plasma.

Convalescent plasma is plasma collected from individuals after resolution of an infection and the development of antibodies. Passive antibody administration by transfusion of convalescent plasma is currently in clinical evaluations to treat COVID-19 patients. The level of neutralizing antibodies vary among convalescent patients and fast and simple methods to identify suitable plasma donations are needed.

A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine.

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S).

Analysis of Humoral Immune Responses in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes coronavirus disease 2019 (COVID-19), a disease of the respiratory system of divergent severity. In the current study, humoral immune responses were characterized in a cohort of 143 patients with COVID-19 from the University Hospital Frankfurt am Main, Germany.

[Monoclonal antibodies for anti-infective therapy].

Sera of animal origin and hyperimmunoglobulins have dominated serum therapy for a century. Although numerous monoclonal antibodies (MABs) have been developed since the end of the 1980s, particularly for the treatment of immunological and oncological diseases, it will take 20 years before the first anti-infective MAB is approved in the European Union. Interestingly, to combat the COVID-19 pandemic, numerous MABs, which are approved in particular for immunological indications, are currently being used to treat the consequences of SARS-CoV‑2 infection, such as pneumonia or hyperimmune reactions.

Analysis of Humoral Immune Responses in Chikungunya Virus (CHIKV)-Infected Patients and Individuals Vaccinated With a Candidate CHIKV Vaccine.

Background: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu-like symptoms. The acute symptoms disappear after 1 week, but chronic arthralgia can persist for years. In this study, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed.

A New Host Factor Essential for Chikungunya Virus.

FHL1 has been identified as a host protein that is essential for chikungunya virus (CHIKV) replication. FHL1 interacts with the chikungunya non-structural protein 3, which is thought to recruit cellular proteins to the viral replication complex. Inhibition of this interaction is a promising target for drug development.

Cellular Attachment and Entry Factors for Chikungunya Virus.

Chikungunya virus (CHIKV) is clinically the most relevant member of the genus. Like alphaviruses in general, CHIKV has the capacity to infect a large variety of cells, tissues, and species. This broad host tropism of CHIKV indicates that the virus uses a ubiquitously expressed receptor to infect cells.

Interference with SAMHD1 Restores Late Gene Expression of Modified Vaccinia Virus Ankara in Human Dendritic Cells and Abrogates Type I Interferon Expression.

Attenuated poxviruses like modified vaccinia virus Ankara (MVA) are promising vectors for vaccines against infectious diseases and cancer. However, host innate immune responses interfere with the viral life cycle and also influence the immunogenicity of vaccine vectors. Sterile alpha motif (SAM) domain and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a phosphohydrolase and reduces cellular deoxynucleoside triphosphate (dNTP) concentrations, which impairs poxviral DNA replication in human dendritic cells (DCs).

Establishment of an Alphavirus-Specific Neutralization Assay to Distinguish Infections with Different Members of the Semliki Forest complex.

Background: Alphaviruses are transmitted by arthropod vectors and can be found worldwide. Alphaviruses of the Semliki Forest complex such as chikungunya virus (CHIKV), Mayaro virus (MAYV) or Ross River virus (RRV) cause acute febrile illness and long-lasting arthralgia in humans, which cannot be clinically discriminated from a dengue virus or Zika virus infection. Alphaviruses utilize a diverse array of mosquito vectors for transmission and spread.

Defining a correlate of protection for chikungunya virus vaccines.

Chikungunya virus infection causes a debilitating febrile illness that in many affected individuals is associated with long-term sequelae that can persist for months or years. Over the past decade a large number of candidate vaccines have been developed, several of which have now entered clinical trials. The rapid and sporadic nature of chikungunya outbreaks poses challenges for planning of large clinical efficacy trials suggesting that licensure of chikungunya vaccines may utilize non-traditional approval pathways based on identification of immunological endpoint(s) predictive of clinical benefit.