Biology subjects

Palese, P.

Publications and source records attributed to Palese, P..

11 recordsLinked to original sources

bioRxiv2025

Addressing SARS-CoV-2 Evolution: Neutralization of Emerging Variants of Concern by the AVX/COVID-12 'Patria' Vaccine Based on HexaPro-S Ancestral Wuhan Spike or Its Updated BA.2.75.2 Version

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global health challenge, causing severe morbidity and mortality, particularly in vulnerable groups such as the elderly, immunocompromised individuals, and those with comorbidities. In low- and middle-income countries (LMICs), vaccine access is hindered by high costs and inequitable distribution. To tackle these issues, Mexico developed the AVX/COVID-12 (V-Wu) vaccine, a recombinant Newcastle disease virus (NDV)-based platform expressing a stabilized ancestral Wuhan spike protein (HexaPro-S). Locally manufactured after rigorous testing and regulatory approval, V-Wu aims to enhance self-sufficiency and equity in immunization. This study evaluates an updated vaccine version, AVX/COVID-12 (V-BA), designed to combat Omicron subvariants by expressing the HexaPro-S protein of BA.2.75.2. Both vaccines were administered intramuscularly in K18-hACE2 transgenic and BALB/c mouse models using a prime-boost regimen. Immunogenicity was analyzed by measuring antibodies against Omicron S proteins BA.2.75.2 and XBB.1.5, as well as neutralizing antibodies against Wuhan, BA.1, XBB.1.16, and JN.1 variants. Both vaccines were safe, eliciting robust antibody responses against Omicron S proteins and neutralizing antibodies against multiple emerging SARS-CoV-2 variants of concern (VOCs). V-BA demonstrated superior protection against current Omicron variants, while V-Wu offered broader coverage, including the ancestral Wuhan strain and emerging variants like JN.1. These findings underscore the adaptability of NDV-based platforms in addressing the evolving SARS-CoV-2 landscape and reaffirm the ongoing utility of the ancestral Patria vaccine. Together, they demonstrate the potential of these platforms to drive the development of next-generation vaccines tailored to emerging viral threats, contributing to global health equity.

immunology↗

bioRxiv2024

Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated

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.

immunology↗

bioRxiv2022

Antigenic landscape analysis of individuals vaccinated with a universal influenza virus vaccine candidate reveals induction of cross-subtype immunity

Current influenza virus vaccines have to be closely matched to circulating strains to provide good protection and antigenic drift and emerging pandemic influenza virus strains present a difficult challenge for them. Universal influenza virus vaccines, including chimeric hemagglutinin (cHA)-based constructs that target the conserved stalk domain of hemagglutinin, are in clinical development. Due to the conservation of the stalk domain, antibodies directed to it show broad binding profiles, usually within group 1 and group 2 influenza A or influenza B virus phylogenies. However, determining the binding breadth of these antibodies with commonly used immunological methods can be challenging. Here, we analyzed serum samples from a phase I clinical trial (CVIA057, NCT03300050) using an influenza virus protein microarray (IVPM). The IVPM technology allowed us to assess immune responses not only to a large number of group 1 hemagglutinins but also group 2 and influenza B hemagglutinins. In CVIA057, different vaccine modalities including a live attenuated influenza virus vaccine and inactivated influenza virus vaccines with or without adjuvant, all in the context of cHA constructs, were tested. We found that vaccination with adjuvanted, inactivated vaccines induced a very broad antibody response covering group 1 hemagglutinins, with limited induction of antibodies to group 2 hemagglutinins. Our data show that cHA constructs do indeed induce very broad immune responses and that the IVPM technology is a useful tool to measure this breadth that broadly protective or universal influenza virus vaccines aim to induce. ImportanceThe development of a universal influenza virus vaccine that protects against seasonal drifted, zoonotic or emerging pandemic influenza viruses would be an extremely useful public health tool. Here we test a technology designed to measure the breadth of antibody responses induced by this new class of vaccines.

microbiology↗

bioRxiv2022

Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice

Equitable access to vaccines is necessary to limit the global impact of the coronavirus disease 2019 (COVID-19) pandemic and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In previous studies, we described the development of a low-cost vaccine based on a Newcastle Disease virus (NDV) expressing the prefusion stabilized spike protein from SARS-CoV-2, named NDV-HXP-S. Here, we present the development of next-generation NDV-HXP-S variant vaccines, which express the stabilized spike protein of the Beta, Gamma and Delta variants of concerns (VOC). Combinations of variant vaccines in bivalent, trivalent and tetravalent formulations were tested for immunogenicity and protection in mice. We show that the trivalent preparation, composed of the ancestral Wuhan, Beta and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant.

immunology↗

bioRxiv2022

Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants

The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of Spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.

microbiology↗

bioRxiv2021

A Newcastle disease virus-vector expressing a prefusion-stabilized spike protein of SARS-CoV-2 induces protective immune responses against prototype virus and variants of concern in mice and hamsters

Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.

immunology↗

bioRxiv2021

Prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine.

The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 ({Delta}NS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of {Delta}NS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a {Delta}NS1 virus results in an immediate antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that {Delta}NS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on {Delta}NS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

microbiology↗

bioRxiv2021

An egg-derived sulfated N-Acetyllactosamine glycan is an antigenic decoy of influenza virus vaccines

Influenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess differential glycosylation patterns than viruses circulating amongst humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived sulfated N-acetyllactosamine (LacNAc) that is an antigenic decoy. Half of subjects that received an egg-grown vaccine mounted an antibody response against this egg-derived antigen. Egg-binding monoclonal antibodies specifically bind viruses grown in eggs, but not viruses grown in other chicken derived cells, suggesting only egg-grown vaccines can induce anti-LacNAc antibodies. Notably, antibodies against the sulfated LacNAc utilized a restricted antibody repertoire and possessed features of natural antibodies, as most antibodies were IgM and have simple heavy chain complementarity determining region 3. By analyzing a public dataset of influenza virus vaccine induced plasmablasts, we discovered egg-binding public clonotypes that were shared across studies. Together, this study shows that egg-grown vaccines can induce antibodies against an egg-associated glycan, which may divert the host immune response away from protective epitopes.

immunology↗

bioRxiv2021

A public broadly neutralizing antibody class targets a membrane-proximal anchor epitope of influenza virus hemagglutinin

Broadly neutralizing antibodies against influenza virus hemagglutinin (HA) have the potential to provide universal protection against influenza virus infections. Here, we report a distinct class of broadly neutralizing antibodies targeting an epitope toward the bottom of the HA stalk domain where HA is "anchored" to the viral membrane. Antibodies targeting this membrane-proximal anchor epitope utilized a highly restricted repertoire, which encode for two conserved motifs responsible for HA binding. Anchor targeting B cells were common in the human memory B cell repertoire across subjects, indicating pre-existing immunity against this epitope. Antibodies against the anchor epitope at both the serological and monoclonal antibody levels were potently induced in humans by a chimeric HA vaccine, a potential universal influenza virus vaccine. Altogether, this study reveals an underappreciated class of broadly neutralizing antibodies against H1-expressing viruses that can be robustly recalled by a candidate universal influenza virus vaccine.

immunology↗

bioRxiv2020

A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.

microbiology↗

bioRxiv2020

Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as vaccine candidate

Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe spike (S) protein of the SARS-CoV-2 is the major antigen that notably induces neutralizing antibodies to block viral entry. Many COVID-19 vaccines are under development, among them viral vectors expressing the S protein of SARS-CoV-2 exhibit many benefits. Viral vector vaccines have the potential of being used as both live or inactivated vaccines and they can induce Th1 and Th2-based immune responses following different immunization regimens. Additionally, viral vector vaccines can be handled under BSL-2 conditions and they grow to high titers in cell cultures or other species restricted-hosts. For a SARS-CoV-2 vaccine, several viral vectors are being tested, such as adenovirus, measles virus and Modified vaccinia Ankara. Added value of this studyThe NDV vector vaccine against SARS-CoV-2 described in this study has advantages similar to those of other viral vector vaccines. But the NDV vector can be amplified in embryonated chicken eggs, which allows for high yields and low costs per dose. Also, the NDV vector is not a human pathogen, therefore the delivery of the foreign antigen would not be compromised by any pre-existing immunity in humans. Finally, NDV has a very good safety record in humans, as it has been used in many oncolytic virus trials. This study provides an important option for a cost-effective SARS-CoV-2 vaccine. Implications of all the available evidenceThis study informs of the value of a viral vector vaccine against SARS-CoV-2. Specifically, for this NDV based SARS-CoV-2 vaccine, the existing egg-based influenza virus vaccine manufactures in the U.S. and worldwide would have the capacity to rapidly produce hundreds of millions of doses to mitigate the consequences of the ongoing COVID-19 pandemic.

microbiology↗