scholarly journals Longitudinal analysis of human humoral responses after vaccination with a live attenuated V. cholerae vaccine

2021 ◽  
Vol 15 (9) ◽  
pp. e0009743
Author(s):  
Oluwaseyi Adekunle ◽  
Alexandra Dretler ◽  
Robert C. Kauffman ◽  
Alice Cho ◽  
Nadine Rouphael ◽  
...  
Keyword(s):  
Immune Response ◽  
Cholera Toxin ◽  
Diarrheal Disease ◽  
Vaccine Development ◽  
Bacterial Pathogen ◽  
Cholera Vaccine ◽  
Live Attenuated Vaccine ◽  
Mediate Immunity ◽  
One Year

Vibrio cholerae is a bacterial pathogen which causes the severe acute diarrheal disease cholera. Given that a symptomatic incident of cholera can lead to long term protection, a thorough understanding of the immune response to this pathogen is needed to identify parameters critical to the generation and durability of immunity. To approach this, we utilized a live attenuated cholera vaccine to model the response to V. cholerae infection in 12 naïve subjects. We found that this live attenuated vaccine induced durable vibriocidal antibody titers that were maintained at least one year after vaccination. Similar to what we previously reported in infected patients from Bangladesh, we found that vaccination induced plasmablast responses were primarily specific to the two immunodominant antigens lipopolysaccharide (LPS) and cholera toxin (CT). Interestingly, the magnitude of the early plasmablast response at day 7 predicted the serological outcome of vaccination at day 30. However, this correlation was no longer present at later timepoints. The acute responses displayed preferential immunoglobulin isotype usage, with LPS specific cells being largely IgM or IgA producing, while cholera toxin responses were predominantly IgG. Finally, CCR9 was highly expressed on vaccine induced plasmablasts, especially on IgM and IgA producing cells, suggesting a role in migration to the gastrointestinal tract. Collectively, these findings demonstrate that the use of a live attenuated cholera vaccine is an effective tool to examine the primary and long-term immune response following V. cholerae exposure. Additionally, it provides insight into the phenotype and specificity of the cells which likely return to and mediate immunity at the intestinal mucosa. A thorough understanding of these properties both in peripheral blood and in the intestinal mucosae will inform future vaccine development against both cholera and other mucosal pathogens. Trial Registration: NCT03251495.

scholarly journals Protection of Macaca nemestrina from Disease following Pathogenic Simian Immunodeficiency Virus (SIV) Challenge: Utilization of SIV Nucleocapsid Mutant DNA Vaccines with and without an SIV Protein Boost

2000 ◽  
Vol 74 (24) ◽  
pp. 11935-11949 ◽  
Author(s):  
Robert J. Gorelick ◽  
Raoul E. Benveniste ◽  
Jeffrey D. Lifson ◽  
Jason L. Yovandich ◽  
William R. Morton ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Peak Plasma ◽  
Full Range ◽  
Macaca Nemestrina ◽  
Wild Type Virus ◽  
Term Study ◽  
Live Attenuated Vaccine ◽  
Long Term Study ◽  
Immunodeficiency Virus

ABSTRACT Molecular clones were constructed that express nucleocapsid (NC) deletion mutant simian immunodeficiency viruses (SIVs) that are replication defective but capable of completing virtually all of the steps of a single viral infection cycle. These steps include production of particles that are viral RNA deficient yet contain a full complement of processed viral proteins. The mutant particles are ultrastructurally indistinguishable from wild-type virus. Similar to a live attenuated vaccine, this approach should allow immunological presentation of a full range of viral epitopes, without the safety risks of replicating virus. A total of 11 Macaca nemestrina macaques were inoculated with NC mutant SIV expressing DNA, intramuscularly (i.m.) in one study and i.m. and subcutaneously in another study. Six control animals received vector DNA lacking SIV sequences. Only modest and inconsistent humoral responses and no cellular immune responses were observed prior to challenge. Following intravenous challenge with 20 animal infectious doses of the pathogenic SIV(Mne) in a long-term study, all control animals became infected and three of four animals developed progressive SIV disease leading to death. All 11 NC mutant SIV DNA-immunized animals became infected following challenge but typically showed decreased initial peak plasma SIV RNA levels compared to those of control animals (P = 0.0007). In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4+ T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation. Although a subset of immunized and control animals were boosted with SIV(Mne) proteins, no apparent protective benefit was observed. Immunization of macaques with DNA that codes for replication-defective but structurally complete virions appears to protect from or at least delay the onset of AIDS after infection with a pathogenic immunodeficiency virus. With further optimization, this may be a promising approach for vaccine development.

scholarly journals BLV: lessons on vaccine development

Retrovirology ◽  
2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Alejandro Abdala ◽  
Irene Alvarez ◽  
Hélène Brossel ◽  
Luis Calvinho ◽  
Hugo Carignano ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Industrial Development ◽  
Vaccine Development ◽  
Leukemia Virus ◽  
Efficacy And Safety ◽  
Live Attenuated Vaccine ◽  
Inactivated Vaccines ◽  
Infected Cells ◽  
Sterilizing Immunity

Abstract Vaccination against retroviruses is a challenge because of their ability to stably integrate into the host genome, undergo long-term latency in a proportion of infected cells and thereby escape immune response. Since clearance of the virus is almost impossible once infection is established, the primary goal is to achieve sterilizing immunity. Besides efficacy, safety is the major issue since vaccination has been associated with increased infection or reversion to pathogenicity. In this review, we discuss the different issues that we faced during the development of an efficient vaccine against bovine leukemia virus (BLV). We summarize the historical failures of inactivated vaccines, the efficacy and safety of a live-attenuated vaccine and the economical constraints of further industrial development.

scholarly journals Neutrophils Are Essential for Containment of Vibrio cholerae to the Intestine during the Proinflammatory Phase of Infection

2012 ◽  
Vol 80 (8) ◽  
pp. 2905-2913 ◽  
Author(s):  
Jessica Queen ◽  
Karla J. Fullner Satchell
Keyword(s):  
Immune Response ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Innate Immune ◽  
Infection Model ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Live Attenuated Vaccine ◽  
Content Type

ABSTRACTCholera is classically considered a noninflammatory diarrheal disease, in comparison to invasive enteric organisms, although there is a low-level proinflammatory response during early infection withVibrio choleraeand a strong proinflammatory reaction to live attenuated vaccine strains. Using an adult mouse intestinal infection model, this study examines the contribution of neutrophils to host defense to infection. Nontoxigenic El Tor O1V. choleraeinfection is characterized by the upregulation of interleukin-6 (IL-6), IL-10, and macrophage inflammatory protein 2 alpha in the intestine, indicating an acute innate immune response. Depletion of neutrophils from mice with anti-Ly6G IA8 monoclonal antibody led to decreased survival of mice. The role of neutrophils in protection of the host is to limit the infection to the intestine and control bacterial spread to extraintestinal organs. In the absence of neutrophils, the infection spread to the spleen and led to increased systemic levels of IL-1β and tumor necrosis factor alpha, suggesting the decreased survival in neutropenic mice is due to systemic shock. Neutrophils were found not to contribute to either clearance of colonizing bacteria or to alter the local immune response. However, when genes for secreted accessory toxins were deleted, the colonizing bacteria were cleared from the intestine, and this clearance is dependent upon neutrophils. Thus, the requirement for accessory toxins in virulence is negated in neutropenic mice, which is consistent with a role of accessory toxins in the evasion of innate immune cells in the intestine. Overall, these data support that neutrophils impact disease progression and suggest that neutrophil effectiveness can be manipulated through the deletion of accessory toxins.

scholarly journals Göttingen Minipigs as a Model to Evaluate Longevity, Functionality, and Memory of Immune Response Induced by Pertussis Vaccines

2021 ◽  
Vol 12 ◽  
Author(s):  
Céline Vaure ◽  
Véronique Grégoire-Barou ◽  
Virginie Courtois ◽  
Emilie Chautard ◽  
Cyril Dégletagne ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Vaccine Development ◽  
Vaccination Schedule ◽  
Memory B Cells ◽  
Immune Memory ◽  
Preclinical Model ◽  
Göttingen Minipig ◽  
Cellular Immune

Evaluation of the short-term and long-term immunological responses in a preclinical model that simulates the targeted age population with a relevant vaccination schedule is essential for human vaccine development. A Göttingen minipig model was assessed, using pertussis vaccines, to demonstrate that vaccine antigen-specific humoral and cellular responses, including IgG titers, functional antibodies, Th polarization and memory B cells can be assessed in a longitudinal study. A vaccination schedule of priming with a whole cell (DTwP) or an acellular (DTaP) pertussis vaccine was applied in neonatal and infant minipigs followed by boosting with a Tdap acellular vaccine. Single cell RNAsequencing was used to explore the long-term maintenance of immune memory cells and their functionality for the first time in this animal model. DTaP but not DTwP vaccination induced pertussis toxin (PT) neutralizing antibodies. The cellular immune response was also characterized by a distinct Th polarization, with a Th-2-biased response for DTaP and a Th-1/Th-17-biased response for DTwP. No difference in the maintenance of pertussis-specific memory B cells was observed in DTaP- or DTwP-primed animals 6 months post Tdap boost. However, an increase in pertussis-specific T cells was still observed in DTaP primed minipigs, together with up-regulation of genes involved in antigen presentation and interferon pathways. Overall, the minipig model reproduced the humoral and cellular immune responses induced in humans by DTwP vs. DTaP priming, followed by Tdap boosting. Our data suggest that the Göttingen minipig is an attractive preclinical model to predict the long-term immunogenicity of human vaccines against Bordetella pertussis and potentially also vaccines against other pathogens.

HUMORAL AND CELLULAR RESPONSE TO SARS-CoV-2 IN COVID-19 PATIENTS

2021 ◽  
Vol 100 (2) ◽  
pp. 17-21
Author(s):  
A.G. Rumyantsev ◽  
Keyword(s):  
Immune Response ◽  
Cellular Response ◽  
Immune Memory ◽  
Population Immunity ◽  
Coronavirus Infection ◽  
One Year ◽  
And Control ◽  
Long Term Prediction ◽  
Humoral And Cellular Response

The study of the immune response to SARS-CoV-2 is crucial for the prognosis and control of coronavirus infection, diagnosis and formation of individual and population immunity, the development of indications and evaluation of the effectiveness of vaccinations, and, ultimately, the scientific prediction of the course of a pandemic. One year after the infection debuted in numerous immunological studies in COVID-19 patients, kinetics, duration and evolution of immune memory in humans due to infection are not well predictable, as data obtained represent the initial effector phase of the immune response, and the responses after recovery from infection cannot be used for long-term prediction. The paper presents an analysis of the results of studies of immune response and immune memory to SARS-CoV-2, including all three branches of adaptive immunity: immunoglobulins, memory B-cells, CD8+ and CD4+ T-cells in sick and cured patients in the dynamic period of 6–8 months after the onset of the disease.

scholarly journals Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

2020 ◽  
Vol 11 ◽  
Author(s):  
David S. Kim ◽  
Sarah Rowland-Jones ◽  
Ester Gea-Mallorquí
Keyword(s):  
Immune Response ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Adaptive Immune Response ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Global Pandemic ◽  
Human Immune ◽  
Novel Coronavirus

In December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China resulted in the current COVID-19 global pandemic. The human immune system has not previously encountered this virus, raising the important question as to whether or not protective immunity is generated by infection. Growing evidence suggests that protective immunity can indeed be acquired post-infection—although a handful of reinfection cases have been reported. However, it is still unknown whether the immune response to SARS-CoV-2 leads to some degree of long-lasting protection against the disease or the infection. This review draws insights from previous knowledge regarding the nature and longevity of immunity to the related virus, SARS-CoV, to fill the gaps in our understanding of the immune response to SARS-CoV-2. Deciphering the immunological characteristics that give rise to protective immunity against SARS-CoV-2 is critical to guiding vaccine development and also predicting the course of the pandemic. Here we discuss the recent evidence that characterises the adaptive immune response against SARS-CoV-2 and its potential implications for the generation of memory responses and long-term protection.

scholarly journals Memory immune response: a major challenge in vaccination

2012 ◽  
Vol 3 (5) ◽  
pp. 479-486 ◽  
Author(s):  
Antonella Prisco ◽  
Piergiuseppe De Berardinis
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Vaccine Development ◽  
Immune Memory ◽  
Gene Expression Signatures ◽  
Antibody Titers ◽  
Memory Immune Response ◽  
Protective Threshold

AbstractA crucial challenge for vaccine development is to design vaccines that induce a long-lasting protective immune response, i.e., immune memory. The persistence of antigen-specific antibody titers over a protective threshold, and the ability to exibit a ‘recall response’ to a subsequent encounter with an antigen have long been the only measurable correlates of vaccine take and immune memory development, suffering from the disadvantage of relying on long-term monitoring of the immune response. In the last few years, advances in the technologies for the identification and characterization of the cell subsets and molecular pathways involved in the immune response to vaccination have allowed innovative approaches to the identification of early correlates of immune memory. In this review, we discuss recent data and hypotheses on early correlates of the development of immune memory, with special emphasis on the gene expression signatures that underlie the self-renewal ability of some lymphocyte subsets, and their similarities with gene expression signatures in stem cells.

scholarly journals Sero-surveillance and sero-monitoring of locally produced PPR vaccine in the field and experimental level

2016 ◽  
Vol 2 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Md Ehsanul Kabir ◽  
Md Mokbul Hossain ◽  
Md Ershaduzzaman ◽  
Md Abu Yousuf ◽  
Md Rafiqul Islam
Keyword(s):  
Immune Response ◽  
Viral Disease ◽  
High Morbidity ◽  
Live Attenuated Vaccine ◽  
Antibody Titres ◽  
Immunization Study ◽  
Group A ◽  
The Mean ◽  
One Year ◽  
Group B

Peste des Petits Ruminants (PPR) is a highly contagious, economically important viral disease of goats with high morbidity and mortality. To control the disease effectively a live attenuated vaccine is available in Bangladesh which is produced by Livestock Research Institute (LRI), Mohakhali, Dhaka. The study was carried out to determine the immune status and immune response against PPR in field and experimental Black Bengal goats. Sero-surveillance of PPR was conducted by using c-ELISA in non-vaccinated 240 goats in Gazipur, Sirajgonj and Barisal. Out of the 240 goats tested, of which only 39 (20.31%) goats had positive level of PPR antibodies while 16.25% (13 out of 80 goats) in Gazipur, 28.75% (23 out of 80 goats) in Barisal and 3.75% ((3 out of 80 goats)) in Sirajgonj. In case of sero-monitoring of PPR, the result revealed that vaccinated goats from Rajshahi showed high positive result and have higher seroprevalence where 75% (60 out of 80 goats) were seropositive and only 25% (20 out of 80 goats) are seronegative. These result indicated that vaccinated Rajshahi goats is more resistant for PPR virus than non vaccinated goats. In experimentally to perform sero-monitoring, 10 seronegative goats were selected and divided into two equal groups (A and B).The immunization study against PPR with a commercial PPR vaccine was conducted on 5 goats of group A by inoculating @ 1.0 ml vaccine / animal subcutaneously and group B kept as non-vaccinated. The antibody titres against PPR in goats were determined at 0 day on vaccination and after 21DPV, 180DPV and 365DPV. The results found that 100% (5 out 5goats) seronegative in both vaccinated goats of group A and non-vaccinated goats of group B at 0 day on vaccination. The mean negative titres± SD were 79.285±13.921 and 76.707±9.265 in vaccinated group A and group B, respectively. The mean positive titers ±SD were 20.201±2.480, 8.630±4.970 and 11.382±1.419 at 21DPV, 180DPV an 365DPV, respectively in group A (100% seropositive). In case of non-vaccinated group B, the mean negative titres±SD were 74.258±7.793, 77.726±9.142 and 82.965±7.492 at 21DPV, 180DPV and 365DPV, respectively (100% seronegative). As it is observed, the antibody titres remain at the level over the period of time that indicates the immune response against PPR. From this finding, it is said that PPR vaccine could produce immune response in goats for about one year or 365 days.Asian J. Med. Biol. Res. March 2016, 2(1): 33-37

scholarly journals A year-long immune profile of the systemic response in acute stroke survivors

Brain ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 978-991 ◽  
Author(s):  
Amy S Tsai ◽  
Kacey Berry ◽  
Maxime M Beneyto ◽  
Dyani Gaudilliere ◽  
Edward A Ganio ◽  
...  
Keyword(s):  
Immune Response ◽  
Ischaemic Stroke ◽  
Acute Stroke ◽  
Peripheral Blood ◽  
Systemic Response ◽  
Systemic Immune Response ◽  
Adaptive Immune ◽  
One Year ◽  
Immune Profiling

Whether the systemic immune response to stroke contributes to long-term disability is unclear. Using deep immune profiling of peripheral blood over a one-year period following ischaemic stroke, Tsai et al. identify three immunological phases characterized by sequential engagement of innate and adaptive immune compartments, which correlate with post-stroke cognitive trajectories.

Sign in / Sign up

Export Citation Format

Share Document