Nasal vaccine or monoclonal therapy: Which is winning weapon against SARS-CoV-2 variants in 2022?
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ABSTRACT:
SUBMITTER: Lo Muzio L
PROVIDER: S-EPMC9107288 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
Nasal vaccine or monoclonal therapy: Which is winning weapon against SARS-CoV-2 variants in 2022?
Lo Muzio Lorenzo L Spirito Francesca F
Journal of global health 20220514
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Project description:SARS-CoV-2 has caused the COVID-19 pandemic since early 2020. As of January 2022, the worldwide spreading of SARS-CoV-2 leads to approximately 0.35 billion of human infections and five millions of deaths. Current vaccination is one of the effective ways to control SARS-CoV-2 transmission and reduce the disease severity. However, the antibody level against the immunogen significantly drops several months after the standard two-dose vaccination, and hence a third or fourth dose booster (the same immunogen) has been suggested to boost the antibody response. Here, we described an ultra-effective nasal vaccine booster that potently induced the extraordinary high-level of neutralizing antibody in pre-vaccinated mice. The vaccine booster is composed of a recombinant receptor binding domain of SARS-CoV-2 spike (either wild-type or omicron) fused with a domain of SARS-CoV-2 nucleoprotein. In the absence of adjuvants, a single intranasal administration of the booster in pre-vaccinated mice significantly induced systemic and mucosal antibody responses as evidenced by the elevation of the cross-variant neutralizing antibody and induction of IgA in bronchoalveolar lavage respectively. Most importantly, the single dose nasal vaccine booster (omicron version) potently enhanced the neutralizing activity against authentic SARS-CoV-2 omicron virus infection. Taken together, the induction of respiratory mucosal immunity and the enhancement of cross-variant neutralizing activity by the nasal vaccine booster warrants further clinical trials in humans.
| S-EPMC8973333 | biostudies-literature
Project description:Although the antibody response to COVID-19 vaccination has been studied extensively at the polyclonal level using immune sera, little has been reported on the antibody response at the monoclonal level. Here, we isolate a panel of 44 anti-SARS-CoV-2 monoclonal antibodies (mAbs) from an individual who received two doses of the ChAdOx1 nCoV-19 (AZD1222) vaccine at a 12-week interval. We show that, despite a relatively low serum neutralization titer, Spike-reactive IgG+ B cells are still detectable 9 months post-boost. Furthermore, mAbs with potent neutralizing activity against the current SARS-CoV-2 variants of concern (Alpha, Gamma, Beta, Delta, and Omicron) are present. The vaccine-elicited neutralizing mAbs form eight distinct competition groups and bind epitopes overlapping with neutralizing mAbs elicited following SARS-CoV-2 infection. AZD1222-elicited mAbs are more mutated than mAbs isolated from convalescent donors 1-2 months post-infection. These findings provide molecular insights into the AZD1222 vaccine-elicited antibody response.
| S-EPMC9010245 | biostudies-literature
Project description:Although Omicron RBD of SARS-CoV-2 accumulates many mutations, the backbone region (truncated RBD) of spike protein is highly conserved. Here, we designed several subunit vaccines by keeping the conserved spike backbone region of SARS-CoV-2 Omicron BA.1 subvariant (S-6P-no-RBD), or inserting the RBD of Delta variant (S-6P-Delta-RBD), Omicron (BA.5) variant (S-6P-BA5-RBD), or ancestral SARS-CoV-2 (S-6P-WT-RBD) to the above backbone construct, and evaluated their ability to induce immune responses and cross-protective efficacy against various SARS-CoV-2 variants and SARS-CoV. Among the four subunit vaccines, S-6P-Delta-RBD protein elicited broad and potent neutralizing antibodies against all SARS-CoV-2 variants tested, including Alpha, Beta, Gamma, and Delta variants, the BA.1, BA.2, BA.2.75, BA.4.6, and BA.5 Omicron subvariants, and the ancestral strain of SARS-CoV-2. This vaccine prevented infection and replication of SARS-CoV-2 Omicron, and completely protected immunized mice against lethal challenge with the SARS-CoV-2 Delta variant and SARS-CoV. Sera from S-6P-Delta-RBD-immunized mice protected naive mice against challenge with the Delta variant, with significantly reduced viral titers and without pathological effects. Protection correlated positively with the serum neutralizing antibody titer. Overall, the designed vaccine has potential for development as a universal COVID-19 vaccine and/or a pan-sarbecovirus subunit vaccine that will prevent current and future outbreaks caused by SARS-CoV-2 variants and SARS-related CoVs.
| S-EPMC11272943 | biostudies-literature
Project description:The constant mutation of SARS-CoV-2 has led to the emergence of new variants, which call for urgent effective therapeutic interventions. The trimeric spike (S) protein of SARS-CoV-2 is highly immunogenic with the receptor-binding domain (RBD) that binds first to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and is therefore the target of many neutralizing antibodies. In this study, we characterized a broadly neutralizing monoclonal antibody (mAb) 9G8, which shows potent neutralization against the authentic SARS-CoV-2 wild-type (WT), Alpha (B.1.1.7), and Delta (1.617.2) viruses. Furthermore, mAb 9G8 also displayed a prominent neutralizing efficacy in the SARS-CoV-2 surrogate virus neutralization test (sVNT) against the Epsilon (B.1.429/7), Kappa (B.1.617.1), Gamma (P.1), Beta (B.1.351), and Delta Plus (1.617.2.1) RBD variants in addition to the variants mentioned above. Based on our in vitro escape mutant studies, we proved that the mutations V483F and Y489H within the RBD were involved in ACE2 binding and caused the neutralizing evasion of the virus from mAb 9G8. The development of such a cross-reactive neutralizing antibody against majority of the SARS-CoV-2 variants provides an important insight into pursuing future therapeutic agents for the prevention and treatment of COVID-19.
| S-EPMC8878391 | biostudies-literature
Project description:Since the coronavirus disease outbreak in 2019, several antibody therapeutics have been developed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Antibody therapeutics are effective in neutralizing the virus and reducing hospitalization in patients with mild and moderate infections. These therapeutics target the spike protein of SARS-CoV-2; however, emerging mutations in this protein reduce their efficiency. In this study, we developed a universal SARS-CoV-2 neutralizing antibody. We generated a humanized monoclonal antibody, MG1141A, against the receptor-binding domain of the spike protein through traditional mouse immunization. We confirmed that MG1141A could effectively neutralize live viruses, with an EC50 of 92 pM, and that it exhibited effective Fc-mediated functions. Additionally, it retained its neutralizing activity against the alpha (UK), beta (South Africa), and gamma (Brazil) variants of SARS-CoV-2. Taken together, our study contributes to the development of a novel antibody therapeutic approach, which can effectively combat emerging SARS-CoV-2 mutations.
| S-EPMC8637776 | biostudies-literature
Project description:BackgroundSequential infections with SARS-CoV-2 variants such as Alpha, Delta, Omicron and its sublineages may cause high morbidity, so it is necessary to develop vaccines that can protect against both wild-type (WT) virus and its variants. Mutations in SARS-CoV-2's spike protein can easily alter viral transmission and vaccination effectiveness.MethodsIn this study, we designed full-length spike mRNAs for WT, Alpha, Delta, and BA.5 variants and integrated each into monovalent or bivalent mRNA-lipid nanoparticle vaccines. A pseudovirus neutralization assay was conducted on immunized mouse sera in order to examine the neutralizing potential of each vaccine.ResultsMonovalent mRNA vaccines were only effective against the same type of virus. Interestingly, monovalent BA.5 vaccination could neutralize BF.7 and BQ.1.1. Moreover, WT, Alpha, Delta, BA.5, and BF.7 pseudoviruses were broadly neutralized by bivalent mRNA vaccinations, such as BA.5 + WT, BA.5 + Alpha, and BA.5 + Delta. In particular, BA.5 + WT exhibited high neutralization against most variants of concern (VOCs) in a pseudovirus neutralization assay.ConclusionsOur results show that combining two mRNA sequences may be an effective way to develop a broadly protective SARS-CoV-2 vaccine against a wide range of variant types. Importantly, we provide the optimal combination regimen and propose a strategy that may prove useful in combating future VOCs.
| S-EPMC10304269 | biostudies-literature
Project description:IntroductionAppearances of SARS-CoV-2 variants have created havoc and additional challenges for the ongoing vaccination drive against pandemic COVID-19. Interestingly, several vaccine platforms are showing great potential to produce successful vaccines against SARS-CoV-2 and its variants. Billions of COVID-19 vaccine doses have been administered worldwide. Mix-and-Match COVID-19 vaccines involving the mixing of the same platform vaccines and also two different vaccine platforms may provide greater protection against SARS-CoV-2 and its variants. COVID-19 vaccines have become one of the most important tools to mitigate the ongoing pandemic COVID-19.Areas coveredWe describe SARS-Cov-2 variants, their impact on the population, COVID-19 vaccines, diverse vaccine platforms, doses of vaccines, the efficacy of vaccines against SARS-CoV-2 and its variants, mitigation of the COVID-19 transmission- alternatives to vaccines.Expert opinionDiverse vaccine platforms may safeguard against ongoing, deadly SARS-CoV-2 and its infectious variants. The efficacies of COVID-19 vaccines are significantly high after the administration of the second dose. Further, it protects individuals including vulnerable patients with co-morbidities from SARS-CoV-2 and its variants. The hospitalizations and deaths of the individuals may be prevented by COVID-19 vaccines.
| S-EPMC8787839 | biostudies-literature
Project description:Vaccination is the most cost-effective means in the fight against infectious diseases. Various kinds of vaccines have been developed since the outbreak of COVID-19, some of which have been approved for clinical application. Though vaccines available achieved partial success in protecting vaccinated subjects from infection or hospitalization, numerous efforts are still needed to end the global pandemic, especially in the case of emerging new variants. Safe and efficient vaccines are the key elements to stop the pandemic from attacking the world now; novel and evolving vaccine technologies are urged in the course of fighting (re)-emerging infectious diseases. Advances in biotechnology offered the progress of vaccinology in the past few years, and lots of innovative approaches have been applied to the vaccine design during the ongoing pandemic. In this review, we summarize the state-of-the-art vaccine strategies involved in controlling the transmission of SARS-CoV-2 and its variants. In addition, challenges and future directions for rational vaccine design are discussed.
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Project description:SARS-CoV-2 transmission in Western Australia, Australia, was negligible until a wave of Omicron variant infections emerged in February 2022, when >90% of adults had been vaccinated. This unique pandemic enabled assessment of SARS-CoV-2 vaccine effectiveness (VE) without potential interference from background immunity from prior infection. We matched 188,950 persons who had a positive PCR test result during February-May 2022 to negative controls by age, week of test, and other possible confounders. Overall, 3-dose VE was 42.0% against infection and 81.7% against hospitalization or death. A primary series of 2 viral-vectored vaccines followed by an mRNA booster provided significantly longer protection against infection >60 days after vaccination than a 3-dose series of mRNA vaccine. In a population free from non-vaccine-derived background immunity, vaccines against the ancestral spike protein were ≈80% effective for preventing serious outcomes from infection with the SARS-CoV-2 Omicron variant.
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Project description:The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had become a global concern because of its unexpectedly high pathogenicity and transmissibility. SARS-CoV-2 variants that reduce the immune protection elicited from previous vaccination or natural infection raise challenges in controlling the spread of the pandemic. The development of universal vaccines against these variants seems to be a practical solution to alleviate the physical and economic effects caused by this disease, but it is hard to achieve. In this review, we describe the high mutation rate of RNA viruses and dynamic molecular structures of SARS-CoV-2 variants in several major neutralizing epitopes, trying to answer the question of why universal vaccines are difficult to design. Understanding the biological basis of immune evasion is crucial for combating these obstacles. We then summarize several advancements worthy of further study, including heterologous prime-boost regimens, construction of chimeric immunogens, design of protein nanoparticle antigens, and utilization of conserved neutralizing epitopes. The fact that some immunogens can induce cross-reactive immune responses against heterologous coronaviruses provides hints for universal vaccine development. We hope this review can provide inspiration to current universal vaccine studies.
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