PaxVax CVD 103-HgR single-dose live oral cholera vaccine

Levine, Myron M.; Chen, Wilbur H.; Kaper, James B.; Lock, Michael; Danzig, Lisa; Gurwith, Marc

doi:10.1080/14760584.2017.1291348

Cited by 60 publications

(55 citation statements)

References 75 publications

(120 reference statements)

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“…The successful vaccine licensure by the FDA of the PaxVax CVD 103-HgR (Vaxchora ® ) vaccine after a trial at UMB-CVD evaluating the efficacy against human experimental infection with Vibrio cholera O1 El Tor presents a model of human experimental infection as a pathway to licensure. 54,55 However, licensure of a malaria vaccine will require a combination of CHMI and field trials and will not be as straightforward as cholera, given the heterogeneity of malaria in endemic countries. It is also not clear as to how many challenge strains would adequately represent the diversity of epitopes seen immunologically after exposure in malaria-endemic regions.…”

Section: Discussionmentioning

confidence: 99%

The Controlled Human Malaria Infection Experience at the University of Maryland

Friedman-Klabanoff

Laurens

Berry

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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Controlled human malaria infection (CHMI) is a powerful tool to evaluate the efficacy of malaria vaccines and pharmacologics. Investigators at the University of Maryland, Baltimore, Center for Vaccine Development (UMB-CVD) pioneered the technique in the 1970s and continue to advance the frontiers of CHMI research. We reviewed the records of 338 malaria-naive volunteers who underwent CHMI at UMB-CVD with Plasmodium falciparum from 1971 until 2017. These 338 volunteers underwent 387 CHMI events, including 60 via intradermal injection or direct venous inoculation (DVI) of purified, cryopreserved sporozoites. No volunteer suffered an unplanned hospitalization or required intravenous therapy related to CHMI. Median prepatency period was longer in challenges using NF54 (9 days) than in those using 7G8 (8 days), P = 0.0006 by the log-rank test. With dose optimization of DVI, the prepatent period did not differ between DVI and mosquito bite challenge (log-rank test, P = 0.66). Polymerase chain reaction (PCR) detected P. falciparum infection 3 days earlier than thick smears (P < 0.001), and diagnosis by ultrasensitive PCR was associated with less severe symptoms than smear-based diagnosis (39% versus 0%, P = 0.0003). Historical studies with NF54 showed a shorter median prepatency period of 10.3 days than more recent studies (median 11.0 days, P = 0.02) despite significantly lower salivary gland scores in earlier studies, P = 0.0001. The 47-year experience of CHMI at UMB-CVD has led to advancements in sporozoite delivery, diagnostics, and use of heterologous challenge. Additional studies on new challenge strains and genomic data to reflect regional heterogeneity will help advance the use of CHMI as supporting data for vaccine licensure.

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Section: Discussionmentioning

confidence: 99%

The Controlled Human Malaria Infection Experience at the University of Maryland

Friedman-Klabanoff

Laurens

Berry

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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“…There is no live-attenuated OCV licensed for use in cholera-endemic regions. The only clinically available live-attenuated OCV is Vaxchora (CVD103-HgR), which is derived from a classical O1 Inaba V. cholerae strain and was approved by the US FDA in 2017 for use in travelers [24]. In contrast to killed OCVs, live vaccines, such as CVD103-HgR and the El Tor-derived vaccine Peru-15, elicit more potent immune responses in young children [25,26], potentially because they more closely mimic natural infection than killed OCVs.…”

Section: Introductionmentioning

confidence: 99%

Oral immunization with a probiotic cholera vaccine induces broad protective immunity againstVibrio choleraecolonization and disease in mice

Sit

Zhang

Fakoya

et al. 2019

Preprint

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23Oral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations 24 generally require multiple doses and lack efficacy in young children. We recently developed a 25 new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during 26 the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant 27 rabbits, preventing intestinal colonization and disease by wild-type V. cholerae before the onset 28 of adaptive immunity. However, it remained unknown whether HaitiV would behave similarly to 29 other OCVs to stimulate adaptive immunity against V. cholerae. Here, we orally immunized adult 30 germ-free female mice to test HaitiV's immunogenicity. HaitiV safely and stably colonized 31 vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 32 days of administration. Pups born to immunized mice were protected against lethal challenges of 33 both homologous and heterologous V. cholerae strains. Cross-fostering experiments revealed 34 that protection was not dependent on vaccine colonization in or transmission to the pups. These 35 findings demonstrate the protective immunogenicity of HaitiV and support its development as a 36 new tool for limiting cholera. 37 38

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“…12 This led to studies of a number of candidate deletion mutants of classical and El Tor V. cholerae O1 designed to produce similar immunity and resulted in the live, attenuated V. cholerae strain CVD 103-HgR as a safe and effective oral vaccine for the prevention of cholera. 13 Clinical trial experience with CVD 103-HgR included administration to more than 27,000 adults and children as young as 3 months of age. [14][15][16][17][18][19][20][21][22][23] CVD 103-HgR was licensed in several countries ex-United States under the trade names Orochol, Orochol E, and Mutachol, and more than 500,000 commercial doses of CVD 103-HgR vaccine were sold with an indication in travelers aged 2 years or older.…”

Section: Introductionmentioning

confidence: 99%

“…Because SVA seroconversion following PXVX0200 vaccination was a strong correlate of protection in the adult challenge study, the FDA accepted that this measure could be used to bridge immunogenicity and presume efficacy in a pediatric population in an industrialized country. 13 Therefore, this phase 4 study was performed to assess the safety, immunogenicity, and tolerability of a single oral dose of PXVX0200 in children and adolescents in a developed country and to bridge immunogenicity in children and adolescents to adults aged 18-45 years from the lot consistency study. 28…”

Section: Introductionmentioning

confidence: 99%

Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children and Adolescents Aged 6–17 Years

McCarty

Gierman

Bedell

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, redeveloped as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera-induced diarrhea in adult volunteer challenge trials but has not been studied in children in developed countries. We performed a phase 4, placebo-controlled, double-blind, multicenter study to assess the safety, immunogenicity, and tolerability of a single, oral dose of PXVX0200 in children and adolescents aged 6-17 years in the United States and bridged immunogenicity to adults aged 18-45 years from a separate lot consistency study. Volunteers were randomized to receive a single dose of 1 × 10 9 colony forming units (CFU) of PXVX0200 or placebo. Immunogenicity endpoints included SVA levels on days 1, 11, and 29 in volunteers aged 6-17 years and also on days 91 and 181 in volunteers aged 12-17 years. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events (AEs) through day 29, and serious AEs through day 181. A total of 374 participants were enrolled, comprising 321 vaccine and 53 placebo recipients. The SVA seroconversion rates 10 days after immunization were 98.6% and 2.1% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in adults aged 18-45 years. Most reactogenicity was mild to moderate, and there were no vaccine-related serious AEs. The complete dose was consumed in 95.3% and 98.1% of vaccine and placebo recipients, respectively. PXVX0200 appears safe, immunogenic, and well tolerated in children and adolescents aged 6-17 years.

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PaxVax CVD 103-HgR single-dose live oral cholera vaccine

Cited by 60 publications

References 75 publications

The Controlled Human Malaria Infection Experience at the University of Maryland

The Controlled Human Malaria Infection Experience at the University of Maryland

Oral immunization with a probiotic cholera vaccine induces broad protective immunity againstVibrio choleraecolonization and disease in mice

Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children and Adolescents Aged 6–17 Years

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