scholarly journals Protective Immunity against Vibrio harveyi in Grouper Induced by Single Vaccination with Poly (Lactide-co-glycolide) Microparticles Releasing Pleurocidin Peptide and Recombinant Glyceraldehyde-3-phosphate Dehydrogenase

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 33
Author(s):  
Shang-Pin Liu ◽  
Shu-Chun Chuang ◽  
Chung-Da Yang

The peptide adjuvant, pleurocidin (PLE), and the Vibrio harveyi antigen, recombinant glyceraldehyde-3-phosphate dehydrogenase (rGAPDH) protein, were encapsulated with poly (lactide-co-glycolide) (PLG) polymers in our previous study to produce PLG-encapsulated PLE plus rGAPDH microparticles (PLG-PLE/rGAPDH MPs) that sustained stable release of both PLE and rGAPDH as well as, after two-time vaccination with MPs, generated long-term protective immunity against V. harveyi in grouper. Stable controlled-release of PLE plus rGAPDH from PLG-PLE/rGAPDH MPs is an attractive feature for developing an effective single-dose vaccine. In the present study, therefore, we aim to evaluate whether single administration with PLG-PLE/rGAPDH MPs in grouper would result in protective immunity against V. harveyi. Peritoneal vaccination of grouper with one dose of PLG-PLE/rGAPDH MPs raised serum titers over a long 12-week period. Moreover, twelve weeks after vaccination, significant lymphocyte proliferation and maximum TNF-α production were found in grouper immunized with a single dose of PLG-PLE/rGAPDH MPs. More importantly, immune responses elicited by single vaccination with PLG-PLE/rGAPDH MPs protected 80% of fish against a lethal peritoneal challenge of the highly virulent V. harveyi (Vh MML-1). In conclusion, our data truly reveal the feasibility of the development of a single-dose vaccine against V. harveyi based on PLG-PLE/rGAPDH MPs.

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Ana A. Weil ◽  
Crystal N. Ellis ◽  
Meti D. Debela ◽  
Taufiqur R. Bhuiyan ◽  
Rasheduzzaman Rashu ◽  
...  

ABSTRACT Vibrio cholerae infection provides long-lasting protective immunity, while oral, inactivated cholera vaccines (OCV) result in more-limited protection. To identify characteristics of the innate immune response that may distinguish natural V. cholerae infection from OCV, we stimulated differentiated, macrophage-like THP-1 cells with live versus heat-inactivated V. cholerae with and without endogenous or exogenous cholera holotoxin (CT). Interleukin 23A gene (IL23A) expression was higher in cells exposed to live V. cholerae than in cells exposed to inactivated organisms (mean change, 38-fold; 95% confidence interval [95% CI], 4.0 to 42; P < 0.01). IL-23 secretion was also higher in cells exposed to live V. cholerae than in cells exposed to inactivated V. cholerae (mean change, 5.6-fold; 95% CI, 4.4 to 11; P < 0.001). This increase in IL-23 secretion was more marked than for other key innate immune cytokines (e.g., IL-1β and IL-6) and dependent on exposure to the combination of both live V. cholerae and CT. While IL-23 secretion was reduced following stimulation with either heat-inactivated wild-type V. cholerae or a live isogenic ctxAB mutant of V. cholerae, the addition of exogenous CT restored IL-23 secretion in combination with the live isogenic ctxAB mutant V. cholerae, but not when it was paired with stimulation by heat-inactivated V. cholerae. The posttranslational regulation of IL-23 under these conditions was dependent on the activity of the cysteine protease cathepsin B. In humans, IL-23 promotes the differentiation of Th17 cells to T follicular helper cells, which maintain and support long-term memory B cell generation after infection. Based on these findings, the stimulation of IL-23 production may be a determinant of protective immunity following V. cholerae infection. IMPORTANCE An episode of cholera provides better protection against reinfection than oral cholera vaccines, and the reasons for this are still under study. To better understand this, we compared the immune responses of human cells exposed to live Vibrio cholerae with those of cells exposed to heat-killed V. cholerae (similar to the contents of oral cholera vaccines). We also compared the effects of active cholera toxin and the inactive cholera toxin B subunit (which is included in some cholera vaccines). One key immune signaling molecule, IL-23, was uniquely produced in response to the combination of live bacteria and active cholera holotoxin. Stimulation with V. cholerae that did not produce the active toxin or was killed did not produce an IL-23 response. The stimulation of IL-23 production by cholera toxin-producing V. cholerae may be important in conferring long-term immunity after cholera.


2008 ◽  
Vol 76 (5) ◽  
pp. 2025-2036 ◽  
Author(s):  
Lauriane E. Quenee ◽  
Claire A. Cornelius ◽  
Nancy A. Ciletti ◽  
Derek Elli ◽  
Olaf Schneewind

ABSTRACT Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.


2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Harsha Fernando ◽  
Pradeep Pushpakumara ◽  
Shyrar Tanussiya ◽  
Achala Kamaladasa ◽  
...  

Abstract As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.


npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Giuseppe Lofano ◽  
Corey P. Mallett ◽  
Sylvie Bertholet ◽  
Derek T. O’Hagan

Abstract Vaccines represent the most successful medical intervention in history, with billions of lives saved. Although multiple doses of the same vaccine are typically required to reach an adequate level of protection, it would be advantageous to develop vaccines that induce protective immunity with fewer doses, ideally just one. Single-dose vaccines would be ideal to maximize vaccination coverage, help stakeholders to greatly reduce the costs associated with vaccination, and improve patient convenience. Here we describe past attempts to develop potent single dose vaccines and explore the reasons they failed. Then, we review key immunological mechanisms of the vaccine-specific immune responses, and how innovative technologies and approaches are guiding the preclinical and clinical development of potent single-dose vaccines. By modulating the spatio-temporal delivery of the vaccine components, by providing the appropriate stimuli to the innate immunity, and by designing better antigens, the new technologies and approaches leverage our current knowledge of the immune system and may synergize to enable the rational design of next-generation vaccination strategies. This review provides a rational perspective on the possible development of future single-dose vaccines.


2004 ◽  
Vol 78 (6) ◽  
pp. 3196-3199 ◽  
Author(s):  
Anjeanette Roberts ◽  
Jon D. Reuter ◽  
Jean H. Wilson ◽  
Stuart Baldwin ◽  
John K. Rose

ABSTRACT We generated an attenuated, recombinant vesicular stomatitis virus (VSV) expressing high levels of the cottontail rabbit papillomavirus (CRPV) L1 protein from an upstream site in the VSV genome. Rabbits vaccinated once with this VSV-L1 recombinant produced high levels of anti-L1 antibody and were completely protected against papilloma formation after challenge with CRPV. In contrast, animals vaccinated only once with a VSV vector expressing lower levels of L1 from a downstream site in the VSV genome generated lower levels of L1 antibody and demonstrated only incomplete protection from papilloma formation after challenge. We conclude that the level of L1 protein expression is critical in generating complete immunity with a single-dose vaccine.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Tomotaka Okamura ◽  
Yuya Shimizu ◽  
Masamitsu N. Asaka ◽  
Tomohiro Kanuma ◽  
Yusuke Tsujimura ◽  
...  

AbstractThe use of an adjuvant in vaccination is thought to be effective for enhancing immune responses to various pathogens. We genetically constructed a live attenuated simian human immunodeficiency virus (SHIV) to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When the macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B had become undetectable, SHIV89.6P was not detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of the pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection.


2022 ◽  
Author(s):  
Nungruthai Suntronwong ◽  
Ritthideach Yorsaeng ◽  
Chompoonut Auphimai ◽  
Thanunrat Thongmee ◽  
Preeyaporn Vichaiwattana ◽  
...  

AbstractImmunity wanes in individuals previously infected with SARS-CoV-2, and vaccinating those individuals may help reduce reinfection. Herein, reactogenicity and immunogenicity following vaccination with inactivated (CoronaVac) and vector-based (ChAdOx1-S, AZD1222) vaccines were examined in previously infected individuals. Immune response was also compared between short and long intervals between first date of detection and vaccination. Adverse events were mild but were higher with AZD1222 than with CoronaVac. Baseline IgG-specific antibodies and neutralizing activity were significantly higher with shorter than longer intervals. With a single-dose vaccine, IgG and IgA-specific binding antibodies, neutralizing activity, and total interferon-gamma response peaked at 14 days. Immune response was significantly higher in recovered individuals than in infection-naïve individuals. Antibody response was greater with longer than shorter intervals. AZD1222 induced higher antibody and T cell responses than those of CoronaVac. Thus, to achieve immunity, individuals with prior SARS-CoV-2 exposure may require only a single dose of AZD1222 or two doses of CoronaVac to achieve the immune response. These findings supported vaccine strategies in previously infected individuals.


2021 ◽  
Author(s):  
Gathsaurie Malavige ◽  
Chandima Jeewandara ◽  
Harsha Fernando ◽  
Pradeep Darshana Pushpakumara ◽  
Shyrar Tanussiya ◽  
...  

Abstract As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.


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