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INTRODUCTION: Middle East respiratory syndrome coronavirus (MERS-CoV) causes high mortality in humans. No vaccines are approved for use in humans; therefore, a consistent effort to develop safe and effective MERS vaccines is needed. AREAS COVERED: This review describes the structure of MERS-CoV and the function of its proteins, summarizes MERS vaccine candidates under preclinical study (based on spike and non-spike structural proteins, inactivated virus, and live-attenuated virus), and highlights potential problems that could prevent these vaccines entering clinical trials. It provides guidance for the development of safe and effective MERS-CoV vaccines. EXPERT OPINION: Although many MERS-CoV vaccines have been developed, most remain at the preclinical stage. Some vaccines demonstrate immunogenicity and efficacy in animal models, while others have potential adverse effects or low efficacy against high-dose or divergent virus strains. Novel strategies are needed to design safe and effective MERS vaccines to induce broad-spectrum immune responses and improve protective efficacy against multiple strains of MERS-CoV and MERS-like coronaviruses with pandemic potential. More funds should be invested to move vaccine candidates into human clinical trials.

Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019‐nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray‐based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections., Research Highlights Respiratory tract viral infection including 2019‐nCoV poses great threats worldwide. Currently available and novel emerging diagnostic methods are summarized for several common respiratory viruses, including influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. This review is aimed to assist researchers and clinicians to develop timely and effective diagnostic strategies to detect respiratory virus infections.

Zika virus (ZIKV) is an arbovirus first discovered in the Americas. ZIKV infection is insidious based on its mild clinical symptoms observed after infection. In Brazil, after 2015, ZIKV infection broke out on a large scale, and many infected pregnant women gave birth to babies with microcephaly. The teratogenic effects of the virus on the fetus and its effects on nerves and the immune system have attracted great attention. Currently, no specific prophylactics or therapeutics are clinically available to treat ZIKV infection. Development of a safe and effective vaccine is essential to prevent the rise of any potential pandemic. In this review, we summarize the latest research on Zika vaccine development based on different strategies, including DNA vaccines, subunit vaccines, live-attenuated vaccines, virus-vector-based vaccines, inactivated vaccines, virus-like particles (VLPs), mRNA-based vaccines, and others. We anticipate that this review will facilitate further progress toward the development of effective and safe vaccines against ZIKV infection.

Flaviviruses include several medically important viruses, such as Zika virus (ZIKV), Dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). They have expanded in geographic distribution and refocused international attention in recent years. Vaccination is one of the most effective public health strategies for combating flavivirus infections. In this review, we summarized virus-like particle (VLP)-based vaccines against the above four mentioned flaviviruses. Potential strategies to improve the efficacy of VLP-based flavivirus vaccines were also illustrated. The applications of flavivirus VLPs as tools for viral detection and antiviral drug screening were finally proposed.

A novel coronavirus, designated as SARS-CoV-2, first emerged in Wuhan City, Hubei Province, China, in late December 2019. The rapidly increasing number of cases has caused worldwide panic. In this review, we describe some currently applied diagnostic approaches, as well as therapeutics and vaccines, to prevent, treat and control further outbreaks of SARS-CoV-2 infection.

Chronic inflammatory autoimmune diseases leading to target tissue destruction and disability are not only causing increase in patients' suffering but also contribute to huge economic burden for the society. General increase in life expectancy and high prevalence of these diseases both in elderly and younger population emphasize the importance of developing safe and effective vaccines. In this review, at first the possible mechanisms and risk factors associated with chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D) are discussed. Current advances in the development of vaccines for such autoimmune diseases, particularly those based on DNA, altered peptide ligands and peptide loaded MHC II complexes are discussed in detail. Finally, strategies for improving the efficacy of potential vaccines are explored.

Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection.

Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259-273, together with the positioning of the galactose moiety of CII259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.

Development of effective vaccines, in particular, subunit-based vaccines, against emerging Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) will provide the safest means of preventing the continuous spread of MERS in humans and camels. This review briefly describes the structure of the MERS-CoV spike (S) protein and its receptor-binding domain (RBD), discusses the current status of MERS vaccine development, and illustrates the strategies used to develop RBD-based subunit vaccines against MERS. It also summarizes currently available animal models for MERS-CoV and proposes a future direction for MERS vaccines. Taken together, this review will assist researchers working to develop effective and safe subunit vaccines against MERS-CoV and any other emerging coronaviruses that might cause future pandemics.

Middle East respiratory syndrome (MERS), an emerging infectious disease caused by MERS coronavirus (MERS-CoV), has garnered worldwide attention as a consequence of its continuous spread and pandemic potential, making the development of effective vaccines a high priority. We previously demonstrated that residues 377-588 of MERS-CoV spike (S) protein receptor-binding domain (RBD) is a very promising MERS subunit vaccine candidate, capable of inducing potent neutralization antibody responses. In this study, we sought to identify an adjuvant that optimally enhanced the immunogenicity of S377-588 protein fused with Fc of human IgG (S377-588-Fc). Specifically, we compared several commercially available adjuvants, including Freund's adjuvant, aluminum, Monophosphoryl lipid A, Montanide ISA51 and MF59 with regard to their capacity to enhance the immunogenicity of this subunit vaccine. In the absence of adjuvant, S377-588-Fc alone induced readily detectable neutralizing antibody and T-cell responses in immunized mice. However, incorporating an adjuvant improved its immunogenicity. Particularly, among the aforementioned adjuvants evaluated, MF59 is the most potent as judged by its superior ability to induce the highest titers of IgG, IgG1 and IgG2a subtypes, and neutralizing antibodies. The addition of MF59 significantly augmented the immunogenicity of S377-588-Fc to induce strong IgG and neutralizing antibody responses as well as protection against MERS-CoV infection in mice, suggesting that MF59 is an optimal adjuvant for MERS-CoV RBD-based subunit vaccines.

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".

Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.

Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377–588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.

Amino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PANis highly conserved among different subtypes of influenza virus, which suggests PANto be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PANdomain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation ofin vitroendonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PANwere selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs.

The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines.