scholarly journals Immune Responses in Macaques to a Prototype Recombinant Adenovirus Live Oral Human Papillomavirus 16 Vaccine

2014 ◽  
Vol 21 (9) ◽  
pp. 1224-1231 ◽  
Author(s):  
Michael G. Berg ◽  
Robert J. Adams ◽  
Ratish Gambhira ◽  
Mark C. Siracusa ◽  
Alan L. Scott ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Recombinant Adenovirus ◽  
T Cell Responses ◽  
Transcriptional Unit ◽  
Human Papillomavirus 16 ◽  
Cell Responses ◽  
Cell Immunity

ABSTRACTImmunization with human papillomavirus (HPV) L1 virus-like particles (VLPs) prevents infection with HPV. However, the expense and logistical demands of current VLP vaccines will limit their widespread use in resource-limited settings, where most HPV-induced cervical cancer occurs. Live oral adenovirus vaccines have properties that are well-suited for use in such settings. We have described a live recombinant adenovirus vaccine prototype that produces abundant HPV16 L1 protein from the adenovirus major late transcriptional unit and directs the assembly of HPV16 VLPs in tissue culture. Recombinant-derived VLPs potently elicit neutralizing antibodies in mice. Here, we characterize the immune response to the recombinant after dual oral and intranasal immunization of pigtail macaques, in which the virus replicates as it would in immunized humans. The immunization of macaques induced vigorous humoral responses to adenovirus capsid and nonstructural proteins, although, surprisingly, not against HPV L1. In contrast, immunization elicited strong T-cell responses to HPV VLPs as well as adenovirus virions. T-cell responses arose immediately after the primary immunization and were boosted by a second immunization with recombinant virus. T-cell immunity contributes to protection against a wide variety of pathogens, including many viruses. The induction of a strong cellular response by the recombinant indicates that live adenovirus recombinants have potential as vaccines for those agents. These studies encourage and will inform the continued development of viable recombinant adenovirus vaccines.

scholarly journals Induction of Protective Cytotoxic T Cell Responses in the Presence of High Titers of  Virus-neutralizing Antibodies: Implications for Passive and Active Immunization

1998 ◽  
Vol 187 (4) ◽  
pp. 649-654 ◽  
Author(s):  
Peter Seiler ◽  
Marie-Anne Bründler ◽  
Christine Zimmermann ◽  
Doris Weibel ◽  
Michael Bruns ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Lymphocytic Choriomeningitis ◽  
Active Immunization ◽  
Cytotoxic T Cell ◽  
Protective Antibody ◽  
Cell Responses ◽  
Cell Immunity ◽  
Cytotoxic T Cell Responses

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infections in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred immediate protection against systemic virus spread and controlled the virus below detectable levels. However, presence of protective antibody serum titers did not impair induction of antiviral cytotoxic T lymphocyte (CTL) responses after infection with 102 PFU of LCMV. These CTLs efficiently protected mice independent of antibodies against challenge with LCMV–glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intracerebral challenge with LCMV-WE, whereas transfused antibodies alone did not protect, and in some cases even enhanced, lethal lymphocytic choriomeningitis. Against the cytopathic vesicular stomatitis virus (VSV), specific CTLs and Th cells were induced in the presence of high titers of VSV-neutralizing antibodies after infection with 106 PFU of VSV, but not at lower virus doses. Taken together, preexistent protective antibody titers controlled infection but did not impair induction of protective T cell immunity. This is particularly relevant for noncytopathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccinate against such viruses parallel or sequential passive and active immunization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.

scholarly journals Long-term follow-up of SARS-CoV-2 convalescents reveals distinct magnitude of spike-specific immunity after viral re-exposure and vaccination

2021 ◽  
Author(s):  
Percy Knolle ◽  
Nina Körber ◽  
Alina Priller ◽  
Sarah Yazici ◽  
Tanja Bauer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Specific Immunity ◽  
Cell Immunity

Abstract Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is controlled by the host´s immune response1-4, but longitudinal follow-up studies of virus-specific immunity to evaluate protection from re-infection are lacking. Here, we report the results from a prospective study that started during the first wave of the COVID-19 pandemic in spring 2020, where we identified 91 convalescents from mild SARS-CoV-2 infection among 4554 health care workers. We followed the dynamics and magnitude of spike-specific immunity in convalescents during the spontaneous course over ≥ 9 months, after SARS-CoV-2 re-exposure and after BNT162b2 mRNA vaccination. Virus-neutralizing antibodies and spike-specific T cell responses with predominance of IL-2-secreting polyfunctional CD4 T cells continuously declined over 9 months, but remained detectable at low levels. After a single vaccination, convalescents simultaneously mounted strong antibody and T cell responses against the SARS-CoV-2 spike proteins. In naïve individuals, a prime vaccination induced preferentially IL-2-secreting CD4 T cells that preceded production of spike-specific virus-neutralizing antibodies after boost vaccination. Response to vaccination, however, was not homogenous. Compared to four individuals among 455 naïve vaccinees (0.9%), we identified 5/82 (6.1%) convalescents with a delayed response to vaccination. These convalescents had originally developed dysfunctional spike-specific immune responses after SARS-CoV-2 infection, and required prime and boost vaccination to develop strong spike-specific immunity. Importantly, during the second wave of the COVID-19 pandemic in fall/winter of 2021 and prior to vaccination we detected a surge of virus-neutralizing antibodies consistent with re-exposure to SARS-CoV-2 in 6 out of 82 convalescents. The selective increase in virus-neutralizing antibodies occurred without systemic re-activation of spike-specific T cell immunity, whereas a single BNT162b2 mRNA vaccination sufficed to induce strong spike-specific antibody and systemic T cell responses in the same individuals. These results support the notion that BNT162b2 mRNA vaccination synchronizes spike-specific immunity in all convalescents of mild SARS-CoV-2 infection and may provide additional protection from re-infection by inducing more rigorous stimulation of spike-specific T cell immunity than re-exposure with SARS-CoV-2.

scholarly journals Dose Effects of Recombinant Adenovirus Immunization in Rodents

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 144 ◽  
Author(s):  
Eric A. Weaver
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Recombinant Adenovirus ◽  
T Cell Responses ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Cell Responses ◽  
Immune Correlates ◽  
Cell Immunity ◽  
Dose Dependent

Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very difficult to compare immune responses and vaccine efficacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibody responses at the higher vaccine doses, whereas, the IN immunized mice showed a lower response to the higher rAd vaccine doses. Rats did not show dose-dependent antibody responses to increasing vaccine doses. The IM immunized mice and rats also showed significant dose-dependent T cell responses to the rAd vaccine. However, the T cell immunity plateaued in both mice and rats at 109 and 1010 vp/animal, respectively. Additionally, the highest dose of vaccine in mice and rats did not improve the T cell responses. A final vaccine analysis using a lethal influenza virus challenge showed that despite the differences in the immune responses observed in the mice, the mice had very similar patterns of protection. This indicates that rAd vaccines induced dose-dependent immune responses, especially in IM immunized animals, and that immune correlates are not as predictive of protection as initially thought.

scholarly journals An Adenovirus Vector Expressing FMDV RNA Polymerase Combined with a Chimeric VLP Harboring a Neutralizing Epitope as a Prime Boost Strategy to Induce FMDV-Specific Humoral and Cellular Responses

2021 ◽  
Vol 14 (7) ◽  
pp. 675
Author(s):  
Giselle Rangel ◽  
Verónica Martín ◽  
Juan Bárcena ◽  
Esther Blanco ◽  
Alí Alejo
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Large Scale ◽  
Recombinant Adenovirus ◽  
Protective Efficacy ◽  
Vaccination Strategy ◽  
Adenovirus Vector ◽  
T Cell Responses ◽  
Protective Measure ◽  
Cell Responses

Foot and mouth disease is a highly contagious disease affecting cattle, sheep, and swine among other cloven-hoofed animals that imposes serious economic burden by its direct effects on farm productivity as well as on commerce of farmed produce. Vaccination using inactivated viral strains of the different serotypes is an effective protective measure, but has several drawbacks including a lack of cross protection and the perils associated with the large-scale growth of infectious virus. We have previously developed chimeric virus-like particles (VLPs) bearing an FMDV epitope which induced strong specific humoral responses in vaccinated pigs but conferred only partial protection against homologous challenge. While this and other FMD vaccines under development mostly rely on the induction of neutralizing responses, it is thought that induction of specific T-cell responses might improve both cross protective efficacy as well as duration of immunity. Therefore, we here describe the development of a recombinant adenovirus expressing the highly conserved nonstructural FMDV 3D protein as well as its capacity to induce specific T-cell responses in a murine model. We further describe the generation of an FMDV serotype C-specific chimeric VLP and analyze the immunogenicity of two different prime-boost strategies combining both elements in mice. This combination can effectively induce both humoral and cellular FMDV-specific responses eliciting high titers of ELISA and neutralizing antibodies anti-FMDV as well as a high frequency of IFNγ-secreting cells. These results provide the basis for further testing of this anti FMD vaccination strategy in cattle or pig, two of the most relevant natural host of this pathogen.

scholarly journals SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron

2021 ◽  
Author(s):  
Roanne Keeton ◽  
Marius B Tincho ◽  
Amkele Ngomti ◽  
Richard Baguma ◽  
Ntombi Benede ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
T Cell Responses ◽  
Study Groups ◽  
T Cell Response ◽  
Cell Responses ◽  
Cell Immunity

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

scholarly journals GTL001, a bivalent therapeutic vaccine against human papillomavirus 16 and 18, induces antigen-specific CD8+ T cell responses leading to tumor regression

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0174038 ◽  
Author(s):  
Michaël Esquerré ◽  
Myriam Bouillette-Marussig ◽  
Anne Goubier ◽  
Marie Momot ◽  
Christophe Gonindard ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
Tumor Regression ◽  
Therapeutic Vaccine ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Human Papillomavirus 16 ◽  
Cell Responses
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