ABSTRACT
Introduction. The rapid spread of a new coronavirus infection among populations in many countries worldwide has contributed to the genetic evolution of the virus, resulting in the emergence of multiple genetic variants of the SARSCoV-2 coronavirus. Mutations in the viral genome can affect the ability of the virus to bypass the immune system and complicate development of diagnostic and prophylactic drugs. Data on the neutralizing activity of the sera obtained against previously circulating genetic variants of the virus in relation to current SARS-CoV-2 strains may serve as a scientific basis for the selection of the antigens in vaccine development. The aim of this work was to study cross-reactivity of SARSCoV-2 coronavirus strains belonging to different genetic variants, which were isolated in the territory of the Russian Federation during 2020-2022 in the neutralization reaction using mouse hyperimmune sera. Materials and methods. Ten strains of SARS-CoV-2 coronavirus belonging to different genetic variants were used (three non-VOC strains, alpha, beta, gamma, delta, delta+AY, omicron 1 and omicron 2). The hCoV-19/Australia/VIC01/2020 strain (Wuhan) was included in the study as a prototypical variant. BALBc mice were immunized with inactivated concentrated antigen mixed with a 1:1 adjuvant, which was a virus-like immunostimulatory complex based on Quillaja saponaria (Quillaja saponaria). The antibody titer was determined in the neutralization reaction. Results. Essential decrease of neutralizing ability of antibodies specific to non-vOC genetic variants of SARS-CoV-2 coronavirus was revealed against beta VOC and to a lesser degree against alpha and gamma VOC variants. The differences in the neutralizing activity level of antibodies for alpha and beta VOC variants are not significant among themselves, and with gamma VOC variants - there are no significant differences. Neutralizing ability of antibodies specific to delta VOC against alpha and beta VOC variants decreased 4-fold. Neutralizing activity of sera obtained to omicron 1 and 2 variants in relation to the prototype coronavirus variant was reduced 18-fold, to the gamma variant - 12-fold, to delta variants - more than 30-fold;for other variants it was even lower. Conclusions. The results obtained testify to the presence of cross-reactivity between strains of coronavirus belonging to genetic lines Wuhan, alpha, beta, gamma;it is weaker for delta variants. Mutations in the genome of VOC omicron variants led to a significant decrease in antigenic cross-links with earlier genetic variants of the coronavirus. These findings explain the low efficacy of vaccines based on the Wuhan strain, synthetic immunogens, and recombinant proteins based on it against omicron VOC variants, which have caused a rise in morbidity since early 2022, as well as cases of re-infection of humans with new genetic variants of the coronavirus.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Matrix-M™ adjuvant is a key component of several novel vaccine candidates. The Matrix-M adjuvant consists of two distinct fractions of saponins purified from the Quillaja saponaria Molina tree, combined with cholesterol and phospholipids to form 40-nm open cage-like nanoparticles, achieving potent adjuvanticity with a favorable safety profile. Matrix-M induces early activation of innate immune cells at the injection site and in the draining lymph nodes. This translates into improved magnitude and quality of the antibody response to the antigen, broadened epitope recognition, and the induction of a Th1-dominant immune response. Matrix-M-adjuvanted vaccines have a favorable safety profile and are well tolerated in clinical trials. In this review, we discuss the latest findings on the mechanisms of action, efficacy, and safety of Matrix-M adjuvant and other saponin-based adjuvants, with a focus on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine candidate NVX-CoV2373 developed to prevent coronavirus disease 2019 (COVID-19).
Subject(s)
COVID-19 , Saponins , Vaccines , Humans , COVID-19/prevention & control , SARS-CoV-2 , Adjuvants, ImmunologicABSTRACT
The COVID-19 pandemic has exacerbated the public’s need for effective vaccines. Consequently, significant financial support has been provided to developers of a number of innovative vaccines, including the vaccines with saponin-based adjuvants. In 2021, the World Health Organisation recommended Mosquirix, the first malaria vaccine, which contains a saponin adjuvant. An anti-covid vaccine by Novavax is in the approval phase. A promising approach to vaccine development is presented by the use of virus-like immune-stimulating complexes (ISCOMs) containing saponins and by the creation of combinations of ISCOMs with antigens. The aim of the study was to develop, produce and characterise virus-like immune-stimulating complexes based on saponins of Quillaja saponaria, as well as similar saponins of Russian-sourced Polemonium caeruleum. Materials and methods: The ISCOM adjuvants, Matrix-BQ and Matrix-BP, were produced using liquid chromatography and examined using electron microscopy. Balb/c mice were immunised intraperitoneally and intramuscularly with ISCOM-antigen preparations. Afterwards, the immunised animals were challenged with the influenza virus strain, A/California/4/2009(H1N1)pdm09, adapted and lethal to mice. The serum samples were examined using haemagglutination inhibition (HI) tests. Results: The authors produced the ISCOMs containing saponins of Quillaja saponaria and Polemonium caeruleum. After one intramuscular injection of either of the ISCOM-antigen preparations with 1 µg of each of A/Brisbane/02/2018 (H1N1) pdm09, A/Kansas/14/2017 (H3N2), and B/Phuket/3073/2013 haemagglutinin antigens (HAs), HI tests detected serum antibody titres to the corresponding antigens of ≥1:40. Two intramuscular injections of the ISCOM-antigen preparation containing 50 ng of each of the HAs and Matrix-BQ resulted in a protective response. In some animals, two intraperitoneal injections of ISCOM-antigen preparations resulted in the maximum antibody titre to the A/Kansas/14/2017 (H3N2) vaccine strain of 1:20,480. Two intramuscular injections of a test preparation containing 5 µg, 1 µg, 200 ng, or 50 ng of each of the HAs and Matrix-BQ or a control preparation containing 5 µg, 1 µg, or 200 ng of each of the HAs (commercially available vaccines) to the mice that were afterwards infected with the lethal influenza strain protected the experimental animals from death. Conclusions: The ISCOM-based preparations had high immunostimulatory activity in the mouse-model study. The presented results indicate the potential of further studies of ISCOM-based preparations in terms of both vaccine and immunotherapeutic development.
ABSTRACT
Vaccination is the most effective public health intervention to prevent influenza infections, which are responsible for an important burden of respiratory illnesses and deaths each year. Currently, licensed influenza vaccines are mostly split inactivated, although in order to achieve higher efficacy rates, some influenza vaccines contain adjuvants. Although split-inactivated vaccines induce mostly humoral responses, tailoring mucosal and cellular immune responses is crucial for preventing influenza infections. Quillaja brasiliensis saponin-based adjuvants, including ISCOM-like nanoparticles formulated with the QB-90 saponin fraction (IQB90), have been studied in preclinical models for more than a decade and have been demonstrated to induce strong humoral and cellular immune responses towards several viral antigens. Herein, we demonstrate that a split-inactivated IQB90 adjuvanted influenza vaccine triggered a protective immune response, stronger than that induced by a commercial unadjuvanted vaccine, when applied either by the subcutaneous or the intranasal route. Moreover, we reveal that this novel adjuvant confers up to a ten-fold dose-sparing effect, which could be crucial for pandemic preparedness. Last but not least, we assessed the role of caspase-1/11 in the generation of the immune response triggered by the IQB90 adjuvanted influenza vaccine in a mouse model and found that the cellular-mediated immune response triggered by the IQB90-Flu relies, at least in part, on a mechanism involving the casp-1/11 pathway but not the humoral response elicited by this formulation.