Repeated dose toxicity evaluation of a cold chain-free, live, attenuated oral cholera vaccine in Sprague Dawley rats

Xian, Tew Hui; Parasuraman, Subramani; Kurunathan, S.; Ravichandran, Manickam; Prabhakaran, Guruswamy

doi:10.1016/j.vaccine.2018.12.027

Cited by 5 publications

(7 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rat is a versatile and well characterized model in vaccine toxicology studies [6]. In particular, the adult Sprague Dawley (SD) rat is considered a relevant biological model and has been used extensively to evaluate both intrinsic toxicity and toxicity associated with the immune responses induced by vaccines [9][10][11]. Parameters monitored during repeat-dose studies typically include food and water consumption, body weight, and temperature [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Repeat-Dose Toxicity Study Using the AFPL1-Conjugate Nicotine Vaccine in Male Sprague Dawley Rats

et al. 2019

View full text Add to dashboard Cite

Tobacco smoking is the cause of 20% of Canadian deaths per year. Nicotine vaccines present a promising alternative to traditional smoking cessation products, but to date, no vaccine has been able to move through all phases of clinical trials. We have previously demonstrated that the AFPL1-conjugate nicotine vaccine does not induce systemic or immunotoxicity in a mouse model and that a heterologous vaccination approach is more advantageous than the homologous routes to inducing mucosal and systemic anti-nicotine antibodies. The purpose of this study was to confirm the safety profile of the vaccine in a repeat-dose toxicity study. The heterologous vaccination strategy was again used, and Sprague Dawley rats were administered a dose five times greater than in our previous studies. Physiological conditions, food and water consumption, body temperature, injection site inflammation, relative weights of organs, histopathology, and blood chemistry and hematology were evaluated during the course of the vaccination period to determine the safety of the vaccine. The AFPL1-conjugate nicotine vaccine did not induce clinically relevant changes or induce symptoms that would be associated with toxicity, making it a promising candidate for future investigations.

show abstract

Section: Introductionmentioning

confidence: 99%

Repeat-Dose Toxicity Study Using the AFPL1-Conjugate Nicotine Vaccine in Male Sprague Dawley Rats

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, the use of human PBMC has raised concerns regarding their safety due to the growing demand for clinical use. It is necessary to determine the safe dose and the maximum number of injections that can be administered for effective therapy, as well as to assess toxicity 25 . We have performed both acute and subchronic study of human PBMC in naive rats without immunosuppressant drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Since the wellness status of animals reflected good conditions, this indicates that human PBMC was not toxic 20,26 . The administration of certain compounds may cause some interaction in the hematological and biochemistry system of animals 25 , and hematological parameters are a sensitive indicator of animal health status 20,27 .…”

Section: Discussionmentioning

confidence: 99%

Safety evaluation of human peripheral blood mononuclear cells in naive rats:a chronic toxicitystudy

Supartono

Farida

Suhandono³

et al. 2022

Bangladesh J Med Sci

View full text Add to dashboard Cite

Human peripheral blood mononuclear cells (PBMC) are widely used within tissue engineering therapy, thus, the evaluation of their safety is mandatory. The present study aims to assess the safety of human PBMC transplantations in naive rats in terms of chronic toxicity. Rats received intravenous injections of human PBMC with doses of 105, 106, or 107 cells (n = 5/group/sex) every month for three months without administration of any immunosuppressant drugs. We evaluated clinical, physical, laboratory, and pathology parameters. No morbidity, mortality, or significant differences occurred within all of the tested parameters between control and experimental groups until the finalization of the study. In conclusion, the current work indicates that human PBMC transplantation in naive rats did not induce chronic toxicity reaction. Bangladesh Journal of Medical Science Vol. 21 No. 02 April’22 Page : 373-383

show abstract

“…These histopathological findings were possibly attributed to the 30 doses of vaccine given in daily succession without an interval. In the acute toxicity study, a single dose of the vaccine of up to 1 × 10 7 CFU did not cause any harmful effects or lethality in SD rats ( 8 ). These findings indicated that the vaccine prototype was safe and did not cause any adverse effects or lethality in SD rats.…”

Section: Toxicity Evaluation (Year 2018–2020)mentioning

confidence: 95%

Live, Genetically Attenuated, Cold-Chain-Free Cholera Vaccine—A Research and Development Journey: Light at the End of a Long Tunnel

Ravichandran¹,

Xian²,

Prabhakaran³

et al. 2022

MJMS

Self Cite

View full text Add to dashboard Cite

Cholera, a diarrheal disease caused by Vibrio cholerae (V. cholerae) O139 and O1 strains, remains a public health problem. The existing World Health Organization (WHO)- licenced, killed, multiple-dose oral cholera vaccines demand ‘cold-chain supply’ at 2 °C–8 °C. Therefore, a live, single-dose, cold-chain-free vaccine would relieve significant bottlenecks and costs of cholera vaccination campaigns. Our cholera vaccine development journey started in 2000 at Universiti Sains Malaysia with isolation of the hemA gene from V. cholerae, followed by development of a gene mutant vaccine candidate VCUSM2 against V. cholerae O139 in 2006. In 2010, VCUSM2 reactogenicity was reduced by replacing its two wild-type ctxA gene copies with mutated ctxA to produce strain VCUSM14. Introducing the hemA gene into VCUSM14 created VCUSM14P, a strain with the 5- aminolaevulinic acid (ALA) prototrophic trait and excellent colonisation and immunological properties (100% protection to wild-type challenged rabbits). It was further refined in Asian Institute of Medicine, Science and Technology (AIMST University), with completion of single- and repeated-dose toxicity evaluations in 2019 in Sprague Dawley (SD) rats, followed by development of a novel cold-chain-free VCUSM14P formulation in 2020. VCUSM14P is unique for its intact cholera toxin B, a known mucosal adjuvant. The built-in adjuvant makes VCUSM14P an ideal vaccine delivery platform for emerging diseases (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] and tuberculosis). Our vaccine formulation mimics natural infection, remains non-reactogenic and immunogenic in vivo, and protects against infection and disease. It will also cost less and be less cumbersome to distribute due to its stability at room temperature. These features could revolutionise the outreach of this and other vaccines to meet global immunisation programmes, particularly in low-resourced areas. The next stage of our journey will be meeting the requisite regulatory requirements to produce the vaccine for rollout to countries where it is most needed.

show abstract

Repeated dose toxicity evaluation of a cold chain-free, live, attenuated oral cholera vaccine in Sprague Dawley rats

Cited by 5 publications

References 17 publications

Repeat-Dose Toxicity Study Using the AFPL1-Conjugate Nicotine Vaccine in Male Sprague Dawley Rats

Repeat-Dose Toxicity Study Using the AFPL1-Conjugate Nicotine Vaccine in Male Sprague Dawley Rats

Safety evaluation of human peripheral blood mononuclear cells in naive rats:a chronic toxicitystudy

Live, Genetically Attenuated, Cold-Chain-Free Cholera Vaccine—A Research and Development Journey: Light at the End of a Long Tunnel

Contact Info

Product

Resources

About