Protection of Hamsters Challenged with SARS-CoV-2 Variants of Concern by Two Doses of MVC-COV1901 Vaccine Followed by a Single Dose of Beta Variant Version of MVC-COV1901

The current fight against COVID-19 is compounded by the Variants of Concern (VoCs), which can diminish the effectiveness of vaccines, increase viral transmission and severity of disease. MVC-COV1901 is a protein subunit vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) adjuvanted with CpG 1018 and aluminum hydroxide. Here we used the Delta variant to challenge hamsters innoculated with S-2P based on the ancestral strain or the Beta variant in two-dose or three-dose regimens. Two doses of ancestral S-2P followed by the third dose of Beta variant S-2P was shown to induce the highest neutralizing antibody titer against live SARS-CoV-2 of the ancestral strain as well as all VoCs. All regimens of vaccination were able to protect hamsters from SARS-CoV-2 Delta variant challenge and reduce lung live virus titer. Three doses of vaccination significantly reduced lung viral RNA titer, regardless of using the ancestral or Beta variant S-2P as the third dose. Based on the immunogenicity and viral challenge data, two doses of ancestral S-2P followed by the third dose of Beta variant S-2P could induce broad and potent immune response against the variants.

Safety and Potency of COVIran Barekat Inactivated Vaccine Candidate for SARS-CoV-2: A Preclinical Study

There is an urgent demand to manufacture an effective and safe vaccine to prevent SARS-CoV2 infection, which resulted in a global pandemic. In this study, we developed an inactivated whole-virus SARS-CoV-2 candidate vaccine named COVIran Barekat. Immunization at two different doses (3 microgram or 5 microgram per dose) elicited a high level of SARS-CoV-2 specific neutralizing antibodies in mice, rabbits, and non-human primates. The results show the safety profile in studied animals (include guinea pig, rabbit, mice, and monkeys). Rhesus macaques were immunized with the two-dose of 5 microgram and microgram of the COVIran Barekat vaccine and showed highly efficient protection against 104 TCID50 of SARS-CoV-2 intratracheal challenge compared with the control group. These results highlight the COVIran Barekat vaccine as a potential candidate to induce a strong and potent immune response which may be a promising and feasible vaccine to protect against SARS-CoV2 infection.

Neutralization of SARS-CoV-2 with IgG from COVID-19-convalescent plasma

While there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.8%) had significant neutralizing activity and moderately to potently inhibited SARS-CoV-2 infection in cell-based assays; however, no detectable neutralizing activity was found in 16 cases (37.2%). Approximately half of the patients (~ 41%), who had significant neutralizing activity, lost the neutralization activity within ~ 1 month. Despite the rapid decline of neutralizing activity in plasmas, good amounts of SARS-CoV-2-S1-binding antibodies were persistently seen. The longer exposure of COVID-19 patients to greater amounts of SARS-CoV-2 elicits potent immune response to SARS-CoV-2, producing greater neutralization activity and SARS-CoV-2-S1-binding antibody amounts. The dilution of highly-neutralizing plasmas with poorly-neutralizing plasmas relatively readily reduced neutralizing activity. The presence of good amounts of SARS-CoV-2-S1-binding antibodies does not serve as a surrogate ensuring the presence of good neutralizing activity. In selecting good COVID-19-convalescent plasmas, quantification of neutralizing activity in each plasma sample before collection and use is required.

Anti-CoVid19 plasmid DNA vaccine induces a potent immune response in rodents by Pyro-drive Jet Injector intradermal inoculation

There is an urgent need to limit and stop the worldwide coronavirus disease 2019 (COVID-19) pandemic via quick development of efficient and safe vaccination methods. Plasmid DNA vaccines are one of the most remarkable vaccines that can be developed in a short term. pVAX1-SARS-CoV2-co, which is a plasmid DNA vaccine, was designed to express severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. The produced antibodies lead to Immunoreactions against S protein, anti-receptor-binding-domain, and neutralizing action of pVAX1-SARS-CoV2-co, as confirmed in a previous study. To promote the efficacy of the pVAX1-SARS-CoV2-co vaccine, a pyro-drive jet injector (PJI) was employed. PJI is an injection device that can adjust the injection pressure depending on various target tissues. Intradermally-adjusted PJI demonstrated that pVAX1-SARS-CoV2-co vaccine injection caused a strong production of anti-S protein antibodies, triggered immunoreactions and neutralizing actions against SARS-CoV-2. Moreover, a high dose of pVAX1-SARS-CoV2-co intradermal injection via PJI did not cause any serious disorders in the rat model. Finally, virus infection challenge in mice, confirmed that intradermally immunized (via PJI) mice were potently protected from COVID-19 infection. Thus, pVAX1-SARS-CoV2-co intradermal injection via PJI is a safe and promising vaccination method to overcome the COVID-19 pandemic.

The Inflammasome and Type-2 Immunity in Clostridium difficile Infection

Clostridium difficile (reclassified as “Clostridioides”) is the leading cause of hospital-acquired infections in the United States, and is associated with high-patient mortality and high rates of recurrence. Inflammasome priming and activation by the bacterial toxins, TcdA, TcdB, and C. difficile transferase (CDT), initiates a potent immune response that is characterized by interleukin- (IL) 8, IL-1β, and neutrophil recruitment, and is required for pathogen killing. However, it is becoming clearer that a strong inflammatory response during C. difficile infection can result in host tissue damage, and is associated with worse patient outcome. Recent work has begun to show that a type-2 immune response, most often associated with helminth infections, allergy, and asthma, may be protective during C. difficile infection. While the mechanisms through how this response protect are still unclear, there is evidence that it is mediated through eosinophil activity. This chapter will review the immune response to C. difficile, how the inflammasome signaling during infection can deleterious to the host, as well as the current understanding of a protective type-2 immunity. Understanding the host immune response may help to provide insight into novel approaches to prognosis markers, as well as how treat patient C. difficile infection without, or in addition to, antibiotics.