ABSTRACT
Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. This study analyses the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-{gamma}) in both CD4+ and CD8+ T-cells. In conclusion, the AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Background: The urgent need for safe, effective, and economical coronavirus disease 2019 (COVID-19) vaccines, especially for booster campaigns targeting vulnerable populations, prompted the development of the AVX/COVID-12 vaccine candidate. AVX/COVD-12 is based in a Newcastle disease virus La Sota (NDV-LaSota) recombinant viral vector. This vaccine expresses a stabilized version of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically the ancestral Wuhan strain. The study aimed to assess its safety, immunogenicity, and potential efficacy as an anti-COVID-19 booster vaccine. Methods: In a phase II/III clinical trial conducted from November 9, 2022, to September 11, 2023, a total of 4,056 volunteers were enrolled. Participants received an intramuscular booster dose of either AVX/COVID-12 or AZ/ChAdOx-1-S vaccines. Safety, immunogenicity, and potential efficacy were assessed through various measures, including neutralizing antibody titers, interferon (IFN)-γ-producing CD4+ T cells, and CD8+ T cells. The evaluation also involved immunobridging, utilizing the AZ/ChAdOx-1-S vaccine as an active comparator, and monitoring the incidence of COVID-19 cases. Findings: The AVX/COVID-12 vaccine induced neutralizing antibodies against both the ancestral SARS-CoV-2 and the BA.2 and BA.5 Omicron variants. The geometric mean ratio of neutralizing antibody titers between individuals immunized with the AVX/COVID-12 vaccine and those with the AZ/ChAdOx-1-S vaccine at 14 days is 0.96, with a confidence interval (CI) of 0.85-1.06. The outcome aligns with the non-inferiority criterion recommended by the World Health Organization (WHO), indicating a lower limit of the CI greater than or equal to 0.67. Induction of IFN-γ-producing CD8+ T cells at day 14 post-immunization was exclusively observed in the AVX/COVID-12 group. Finally, a trend suggested a potentially lower incidence of COVID-19 cases in AVX/COVID-12 boosted volunteers compared to AZ/ChAdOx-1-S recipients. Conclusion: The AVX/COVID-12 vaccine proved safe, well-tolerated, and immunogenic. AVX/COVID-12 meets the WHO non-inferiority standard compared to AZ/ChAdOx-1-S. These results strongly advocate for AVX/COVID-12 as a viable booster dose, supporting its utilization in the population.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19 , Newcastle DiseaseABSTRACT
BackgroundThe global inequity in coronavirus disease 2019 (COVID-19) vaccine distribution, primarily affecting low- and middle-income countries (LMICs), highlights the urgent need for innovative and cost-effective vaccine technologies to address availability disparities. This is crucial for achieving and sustaining widespread immunity and protecting vulnerable populations during future booster campaigns. MethodsTo address this need, we conducted a phase II clinical trial evaluating the safety and immunogenicity of the AVX/COVID-12 "Patria" vaccine as a booster dose. The vaccine was administered through both intramuscular (IM) and intranasal (IN) routes to participants who had previously received severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on adenoviral technology, inactivated virus, or mRNA technology. The inclusion criterion involved individuals with initial anti-spike IgG titers below 1,200 U/mL, allowing observation of the booster effect induced by vaccination. ResultsImmunization with AVX/COVID-12 resulted in a significant (>2.5 times) increase in neutralizing antibodies against the original Wuhan strain and variants of concern (VOCs) such as Alpha, Beta, Delta, and Omicron (BA.2 and BA.5). This immune response was accompanied by cellular interferon-gamma (IFN-{gamma}) production, indicating a robust and multifaceted reaction. ConclusionsThe administration of AVX/COVID-12 as a booster dose, whether through IM or IN routes, was safe and well-tolerated. The vaccine extended immune responses not only against the original Wuhan-1 strain but also against various VOCs. Its ability to enhance preexisting immune responses suggests a potential contribution to expanding and sustaining herd immunity within the population.
Subject(s)
Coronavirus Infections , COVID-19 , Newcastle DiseaseABSTRACT
There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
Current medical guidelines consider COVID-19 pregnant women a high-risk group. Physiological gestation down-regulates the immunological response to maintain "maternal-fetal tolerance"; hence, a SARS-CoV-2 infection constitutes a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients a cross-sectional study was conducted. Leukocyte immunophenotype, mononuclear leukocyte response to polyclonal stimulus, and cytokine/chemokine serum concentration were analyzed in pregnant fifteen COVID-19+ and control groups (fifteen non-pregnant COVID-19+, and thirteen pregnant COVID-19- women). Pregnant COVID-19+ patients exhibit lower percentages of monocytes HLA-DR+ compared with control groups. Nevertheless, pregnant COVID-19+ women show a higher percentage of monocytes CD39+ than controls. Furthermore, a higher concentration of TNF-alfa, IL-6, MIP1b, and IL-4 was observed within the pregnant COVID-19+ group. Our result shows that pregnant women express immunological characteristics that potentially mediate the immune response in COVID-19.
Subject(s)
COVID-19ABSTRACT
Background: Until recently, the incidence of COVID-19 was primarily estimated using molecular diagnostic methods. However, it is internationally accepted that the number of cases is vastly underreported using these methods. Antibody prevalence studies estimate cumulative infection incidences and allow monitoring of transmission dynamics, and the presence of neutralizing antibodies in the population.Methods: In February 2020, the Mexican Social Security Institute began conducting anonymous unrelated sampling of residual sera from specimens collected in clinical laboratories and blood banks across all 32 of the country’s states. Sampling was carried out weekly and began 17 days before Mexico’s first officially confirmed case. The 14,515 sera obtained were analyzed by chemiluminescent-linked immunosorbent assay (CLIA) IgG S1/S2 to determine the presence of total IgG antibodies and, later, positive cases using this technique were also analyzed to determine the rate of neutralization using the enzyme-linked immunosorbent assay (ELISA).Findings: We identified 40 CLIA IgG positive cases before the first official report of SARS-CoV-2 infection in Mexico. The national seroprevalence was 3∙5% in February and 21∙7% in August. Neutralizing activity among patients who generate IgG antibodies was 87∙9% in August 2020 and 10∙4% during the overall study period.Interpretation: The actual extent of the SARS-CoV-2 infection in Mexico is 21 times higher than that reported by molecular techniques. Although the general population is still far from achieving herd immunity, epidemiological indicators of disease burden, and fatality should be re-estimated based on serological studies of this type.Funding Statement: National Council of Science and Technology (CONACyT).Declaration of Interests: The authors have no conflicts of interests to declare.Ethics Approval Statement: This protocol was approved by the scientific, ethics, and biosafety committees of the IMSS National Scientific Research Commission (R-785-2020-60).
Subject(s)
COVID-19ABSTRACT
On January 30th, 2020, the WHO declared the outbreak of COVID19, a disease due to the new coronavirus called SARS-CoV-2. Certain comorbidities, symptoms and signs are characteristic of COVID19 in the general population and in pregnant women. However, pregnant women are considered as a high-risk group for COVID19. To know about the frequency of comorbidities, signs and symptoms, the presence of lymphopenia, antibodies response to SARS-CoV2 and cytokine and chemokine serum concentration, six pregnant women with COVID19 were studied at the moment of admission. The lower concentration of CCL17 was detected in the Pregnant COVID19 group, similar concentration of IL-6 was also detected in non-pregnant and pregnant COVID19 patients. Our result show that pregnant and non-pregnant women with COVID19 has similar cytokine profile.
Subject(s)
COVID-19 , LymphopeniaABSTRACT
Within the last 30 years 3 coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2, have evolved and adapted to cause disease and spread amongst the human population. From the three, SARS-CoV-2 has spread world-wide and to July 2020 it has been responsible for more than 11 million confirmed cases and over half a million deaths. In the absence of an effective treatment or vaccine, social distancing has been the most effective measure to control the pandemic. However it has become evident that as the virus spreads the only tool that will allow us to fully control it is an effective vaccine. There are currently more than 150 vaccine candidates in different stages of development using a variety of viral antigens, with the S protein being the most targeted antigen. Although some new experimental evidence suggests cross-reacting responses between coronaviruses are present in the population, it remains unknown whether potential shared antigens between different coronaviruses could provide cross-protection. Given that coronaviruses are emerging pathogens and continue to represent a threat to global health, the development of a SARS-Cov-2 vaccine that could provide universal protection against other coronaviruses should be pushed forward. Here we present a thorough review of reported B and T cell epitopes shared between SARS-CoV-2 and other relevant coronaviruses, in addition we used web-based tools to predict novel B and T cell epitopes that have not been reported before. Analysis of experimental evidence that is constantly emerging complemented with the findings of this study allow us support the hypothesis that cross-reactive responses, particularly those coming from T cells, might play a key role in controlling infection by SARS-CoV-2. We hope that with the evidence presented in this manuscript we provide arguments to encourage the study of cross-reactive responses in order to elucidate their role in immunity to SARS-CoV-2. Finally we expect our findings will aid targeted analysis of antigen-specific immune responses and guide future vaccine design aiming to develop a cross reactive effective vaccine against respiratory diseases caused by coronaviruses.
Subject(s)
Respiratory Tract Diseases , Severe Acute Respiratory SyndromeABSTRACT
Since its emergence, in December 2019, COVID-19 has resulted in more than 12 million people infected and has killed more than 570000. Hypoxemia has been identified as one of the main clinical manifestations of this disease, especially in severe cases. We have previously reported that in critically ill COVID-19 patients there is a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, which, together with mature monocytes and segmented neutrophils, comprise the vast majority of blood cells in these patients. Such an immature myeloid profile may be the result of a physiological response known as emergency myelopoiesis. In the present study, we performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α (HIF1α) mRNA and its transcriptionally regulated genes. HIF1α is a master transcription factor involved in the cellular response to hypoxia. We herein report that these cellular subsets express high levels of HIF1α mRNA and several of their transcriptional targets, including those related to inflammation, such as CXCL8, CXCR1, CXCR2, and CXCR4; those potentially involved in virus sensing, such as TLR2 and TLR4; and those related to metabolism, such as SLC2A3, PFKFB3, PGK1, GAPDH and SOD2. The up-regulation and participation of HIF1α in relevant events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.
Subject(s)
Hypoxia , Hallucinations , COVID-19 , InflammationABSTRACT
SARS-CoV-2, the etiological agent causing COVID-19, has infected more than 8.7 million people with over 461000 deaths worldwide since its emergence in December 2019. Factors for severe disease, such as diabetes, hypertension and obesity have been identified however, the precise pathogenesis is poorly understood. In order to understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. We performed circulating immune cells scRNAseq from five critically ill COVID-19 patients. Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors and activated monocytes predominated. Trajectory with pseudotime analysis supported the finding of immature cell states. Gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to virus and response to type 1 interferon. Lymphoid lineage was scarce. Our results uncover a transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.