Protein-Based Nanoparticle Vaccines for SARS-CoV-2

The pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has upended healthcare systems and economies around the world. Rapid understanding of the structural biology and pathogenesis of SARS-CoV-2 has allowed the development of emergency use or FDA-approved vaccines and various candidate vaccines. Among the recently developed SARS-CoV-2 candidate vaccines, natural protein-based nanoparticles well suited for multivalent antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses are currently being investigated. This mini-review presents recent innovations in protein-based nanoparticle vaccines against SARS-CoV-2. The design and strategy of displaying antigenic domains, including spike protein, receptor-binding domain (RBD), and other domains on the surface of various protein-based nanoparticles and the performance of the developed nanoparticle-based vaccines are highlighted. In the final part of this review, we summarize and discuss recent advances in clinical trials and provide an outlook on protein-based nanoparticle vaccines.

SARS-CoV-2: Emergence of New Variants and Effectiveness of Vaccines

The emergence of SARS-CoV-2 variants may cause resistance at the immunity level against current vaccines. Some emergent new variants have increased transmissibility, infectivity, hospitalization, and mortality. Since the administration of the first SARS-CoV-2 vaccine to a human in March 2020, there is an ongoing global race against SARS-CoV-2 to control the current pandemic situation. Spike (S) glycoprotein of SARS-CoV-2 is the main target for current vaccine development, which can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. The effectiveness of SARS-CoV-2 vaccines and other therapeutics developments are limited by the new emergent variants at the global level. We have discussed the emergent variants of SARS-CoV-2 on the efficacy of developed vaccines. Presently, most of the vaccines have been tremendously effective in severe diseases. However, there are still noteworthy challenges in certifying impartial vaccines; the stories of re-infections are generating more stressful conditions, and this needs further clinical evaluation.

SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants.

Antigenica and Genetic Characterization of Identified Rotavirus Strains in Qatar in Response to Rotarix Vaccine Usage

To identify genetic and antigenic variation in RV in response to vaccine usage. Methods: A total of 231 RV-positive fecal samples were collected from children suffering from AGE during three-year study period between June 2016 and June 2019. The age of the subjects ranged between 2 months and 14 years (median of 16 months). RV genotyping and neutralizing regions, which include both VP4 (Ptype) and VP7 (G type), were amplified and sequenced. We characterized amino acid sequence variability and predicted antigenicity compared to the Rotarix vaccine strain. Phylogenetic analyses were performed using MEGA7.0. Fisher’s exact test was used to run the statistical analysis for the clinical and demographical characteristics of circulating strains. Results: RV infection was most common in children between 3-36 months of age. Among the RV-positive cases, 135 (59.3%) had been vaccinated using either of the RV vaccines available. The number of children vaccinated with one and two-dose was 53 (39.2%) and 82 (60.8%), respectively. The percentage reduction of disease in a vaccinated group of pediatrics compared to an unvaccinated group of pediatrics was 25%. Of these, 108 (78.2%) experienced diarrhea for less than three days, and only eight (6.7%) had diarrhea for more than five days. All vaccinated children showed mild to moderate dehydration except for ten children who were then treated with intravenous fluids. G3 strains were the most strains detected (40%) followed by G2 (17.7%), G4 (16.8%), G9 (15%), G1 (9%), and G8 (0.9%). The dominant RV strains during the study period were G3P [8] (30.8%), G2P [8] (12.3%), G4P [8] (11.7%) and G1P[8] (10.4%). Comparisons of the amino acid residues defining the VP7 and VP4 antigenic domains revealed several mismatches between G1P [8] strains and the G1 and P [8] strains contained in the currently licensed rotavirus vaccines Rotarix. Eighty percent (n=8) of the G1 genotype specimens harbored three amino acid substitutions (N94S, S123N, and M217T) in 7‐ 1a and 7‐ 2b antigenic sites in comparison to the Rotarix vaccine. The P [8] strains with G4 and G9 counterparts showed the highest degree of variation among all specimens with known G genotype. These viruses had 15 and 13 substitutions in their VP4 antigenic epitopes when compared with the P [8] component of the Rotarix vaccines. Conclusion: This study suggests genetic variability in G1 genotype specimens to escape the vaccine-derived immune response. It also identified the wide diversity of circulating RV genotypes in Qatar.

Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray

The current practice for diagnosis of SARS-CoV-2 infection relies on PCR testing of nasopharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk. This testing strategy likely underestimates the true prevalence of infection, creating the need for serologic methods to detect infections missed by the limited testing to date. Here, we describe the development of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A preliminary study of human sera collected prior to the SARS-CoV-2 pandemic demonstrates overall high IgG reactivity to common human coronaviruses and low IgG reactivity to epidemic coronaviruses including SARS-CoV-2, with some cross-reactivity of conserved antigenic domains including S2 domain of spike protein and nucleocapsid protein. This array can be used to answer outstanding questions regarding SARS-CoV-2 infection, including whether baseline serology for other coronaviruses impacts disease course, how the antibody response to infection develops over time, and what antigens would be optimal for vaccine development.

Comparison of the Efficacy of N9 Neuraminidase-specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

The fifth wave of A(H7N9) virus infection in China from 2016 to 2017 caused great concern due to the large number of individuals infected, the isolation of drug-resistant viruses and emergence of highly pathogenic strains. Antibodies against neuraminidase (NA) provide added benefit to hemagglutinin-specific immunity and may be an important contributor to the effectiveness of A(H7N9) vaccines. We generated a panel of mouse monoclonal antibodies (MAbs) to identify antigenic domains on NA of the novel A(H7N9) virus and compared their functional properties. Two major antigenic regions, i.e., the 250-loop and 370/400/430-loop domains, were identified. MAbs 1E8, 2F6, 10F4 and 11B2, which recognize these 2 antigenic domains, were characterized in depth. These 4 MAbs differ in ability to inhibit cleavage of small and large substrates (MU-NANA and fetuin, respectively) in NA inhibition assays. 1E8 and 11B2 did not inhibit NA cleavage of either MU-NANA or fetuin, 2F6 inhibited cleavage of fetuin alone, whereas 10F4 inhibited cleavage of both substrates. All 4 MAbs reduced thein vitrospread of viruses carrying either the wild-type N9 or N9 with antiviral-resistant mutations, but to different degrees. These MAbs have differentin vivoeffectiveness, 10F4 was the most effective in protecting mice against challenge with A(H7N9) virus, 2F6 was less effective and 11B2 failed to protect BALB/c mice at the doses tested. Our study confirms that NA-specific antibodies can protect against A(H7N9) infection, and suggests thatin vitroproperties can be used to rank antibodies with therapeutic potential.IMPORTANCEThe novel A(H7N9) viruses that emerged in China in 2013 continue to infect humans, with a high fatality rate. The most recent outbreak resulted in larger number of human cases than previous epidemic waves. Due to the absence of a licensed vaccine and emergence of drug-resistant viruses, there is a need to develop alternative approaches to prevent or treat A(H7N9) infection. We have made a panel of mouse monoclonal antibodies (MAbs) specific for neuraminidase (NA) of A(H7N9) viruses, some of these MAbs are effective in inhibiting viruses that are resistant to antivirals used to treat A(H7N9) patients. Binding avidity, inhibition of NA activity and plaque formation correlated with the effectiveness of these MAbs to protect mice against lethal A(H7N9) virus challenge. This study identifiesin vitromeasures that can be used to predict thein vivoefficacy of NA-specific antibodies, providing a way to select MAbs for further therapeutic development.

Identification of an antigenic domain in the N-terminal region of avian hepatitis E virus (HEV) capsid protein that is not common to swine and human HEVs

The antigenic domains located in the C-terminal 268 amino acid residues of avian hepatitis E virus (HEV) capsid protein have been characterized. This region shares common epitopes with swine and human HEVs. However, epitopes in the N-terminal 338 amino acid residues have never been reported. In this study, an antigenic domain located between amino acids 23 and 85 was identified by indirect ELISA using the truncated recombinant capsid proteins as coating antigens and anti-avian HEV chicken sera as primary antibodies. In addition, this domain did not react with anti-swine and human HEV sera. These results indicated that the N-terminal 338 amino acid residues of avian HEV capsid protein do not share common epitopes with swine and human HEVs. This finding is important for our understanding of the antigenicity of the avian HEV capsid protein. Furthermore, it has important implications in the selection of viral antigens for serological diagnosis.