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1.
Mol Ther Nucleic Acids ; 34: 102070, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38034030

RESUMO

Intradermal delivery of DNA vaccines via electroporation (ID-EP) has shown clinical promise, but the use of needle electrodes is typically required to achieve consistent results. Here, delivery of a DNA vaccine targeting the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is achieved using noninvasive intradermal vacuum-EP (ID-VEP), which functions by pulling a small volume of skin tissue into a vacuum chamber containing noninvasive electrodes to perform EP at the injection site. Gene expression and immunogenicity correlated with EP parameters and vacuum chamber geometry in guinea pigs. ID-VEP generated potent humoral and cellular immune responses across multiple studies, while vacuum (without EP) greatly enhanced localized transfection but did not improve immunogenicity. Because EP was performed noninvasively, the only treatment site reaction observed was transient redness, and ID-VEP immune responses were comparable to a clinical needle-based ID-EP device. The ID-VEP delivery procedure is straightforward and highly repeatable, without any dependence on operator technique. This work demonstrates a novel, reliable, and needle-free delivery method for DNA vaccines.

2.
Vaccine ; 40(21): 2960-2969, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35428500

RESUMO

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of T cells and antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.


Assuntos
COVID-19 , Vacinas de DNA , Vacinas Virais , Animais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Macaca mulatta , Camundongos , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Vacinação
3.
Cell Rep Med ; 2(10): 100420, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34604818

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health and social and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (i.d.)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system, which are likely important for providing durable protection against COVID-19 disease.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Pulmão/virologia , Linfócitos T/imunologia , Animais , Anticorpos Neutralizantes/sangue , Vacinas contra COVID-19/uso terapêutico , Feminino , Injeções Intradérmicas , Macaca mulatta , Masculino , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/uso terapêutico , Carga Viral
4.
Nat Commun ; 11(1): 2601, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32433465

RESUMO

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.


Assuntos
Antígenos Virais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Enzima de Conversão de Angiotensina 2 , Animais , Anticorpos Neutralizantes/imunologia , Antígenos Virais/química , Vacinas contra COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Mapeamento de Epitopos , Cobaias , Imunidade Humoral , Imunoglobulina G/imunologia , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Coronavírus da Síndrome Respiratória do Oriente Médio , Modelos Animais , Peptidil Dipeptidase A/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Vacinas Virais/química
5.
Vaccine ; 37(7): 903-909, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30661837

RESUMO

The New Zealand White rabbit is a highly accessible animal model which is regularly employed in biomedical research. However, the paucity of rabbit-specific reagents available limits its use in certain fields. Specifically, the lack of a reliable T cell assay has limited its employment in immune prophylactic and therapeutic studies. To address this inadequacy, we have developed an ELISpot assay to detect cellular immune responses (IFN-γ production) after antigenic stimulation. We have applied this assay to model the T cell responses elicited by a DNA vaccine. Immunization with an influenza nucleoprotein (NP) DNA vaccine revealed strong antigen-specific T cell responses in the peripheral blood mononuclear cell population. We believe this is the first report of such an assay in rabbit species, and it will become a useful tool to monitor in vivo responses to vaccines and permit the wider adoption of this model to measure immunological responses.


Assuntos
Antivirais/metabolismo , ELISPOT/métodos , Vacinas contra Influenza/imunologia , Interferon gama/metabolismo , Proteínas de Ligação a RNA/imunologia , Linfócitos T/imunologia , Vacinas de DNA/imunologia , Proteínas do Core Viral/imunologia , Animais , Feminino , Vacinas contra Influenza/administração & dosagem , Leucócitos Mononucleares/imunologia , Proteínas do Nucleocapsídeo , Coelhos , Vacinas de DNA/administração & dosagem
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