Vaccine Research

History of Vaccine Development

===== Genetically Engineered Food Crops As Vaccines ===== ¹⁾

2005 A rice-based edible vaccine expressing multiple T cell epitopes

A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17525-30.

doi: 10.1073/pnas.0503428102. Epub 2005 Nov 8.

Authors Hidenori Takagi 1 , Takachika Hiroi, Lijun Yang, Yoshifumi Tada, Yoshikazu Yuki, Kaoru Takamura, Ryotaro Ishimitsu, Hideyuki Kawauchi, Hiroshi Kiyono, Fumio Takaiwa

Affiliation

1 Plant Biotechnology Department, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan.

PMID: 16278301 PMCID: PMC1297655 DOI: 10.1073/pnas.0503428102

Abstract

Peptide immunotherapy using multiple predominant allergen-specific T cell epitopes is a safe and promising strategy for the control of type I allergy. In this study, we developed transgenic rice plants expressing mouse dominant T cell epitope peptides of Cry j I and Cry j II allergens of Japanese cedar pollen as a fusion protein with the soybean seed storage protein glycinin. Under the control of the rice seed storage protein glutelin GluB-1 promoter, the fusion protein was specifically expressed and accumulated in seeds at a level of 0.5% of the total seed protein.

Oral feeding to mice of transgenic rice seeds expressing the T cell epitope peptides of Cry j I and Cry j II before systemic challenge with total protein of cedar pollen inhibited the development of allergen-specific serum IgE and IgG antibody and CD4(+) T cell proliferative responses. The levels of allergen-specific CD4(+) T cell-derived allergy-associated T helper 2 cytokine production of IL-4, IL-5, and IL-13 and histamine release in serum were significantly decreased.

Moreover, the development of pollen-induced clinical symptoms was inhibited in our experimental sneezing mouse model. These results indicate the potential of transgenic rice seeds in production and mucosal delivery of allergen-specific T cell epitope peptides for the induction of oral tolerance to pollen allergens. Publication types

Comparative Study Research Support, Non-U.S. Gov't ²⁾

2007 Rice-based mucosal vaccine as a global strategy against bioterrorism

Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination Tomonori Nochi, Hidenori Takagi, Yoshikazu Yuki, +10 , Lijun Yang, Takehiro Masumura, Mio Mejima, Ushio Nakanishi, Akiko Matsumura, Akihiro Uozumi, Takachika Hiroi, Shigeto Morita, Kunisuke Tanaka, Fumio Takaiwa, and Hiroshi Kiyono kiyono@ims.u-tokyo.ac.jp -10Authors Info & Affiliations June 26, 2007 104 (26) 10986-10991 https://doi.org/10.1073/pnas.0703766104

Abstract Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control of infectious diseases. In this study, we developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) under the control of the endosperm-specific expression promoter 2.3-kb glutelin GluB-1 with codon usage optimization for expression in rice seed.

An average of 30 μg of CTB per seed was stored in the protein bodies, which are storage organelles in rice. When mucosally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches and induced CTB-specific serum IgG and mucosal IgA antibodies with neutralizing activity. When expressed in rice, CTB was protected from pepsin digestion in vitro.

Rice-expressed CTB also remained stable and thus maintained immunogenicity at room temperature for >1.5 years, meaning that antigen-specific mucosal immune responses were induced at much lower doses than were necessary with purified recombinant CTB. Because they require neither refrigeration (cold-chain management) nor a needle, these rice-based mucosal vaccines offer a highly practical and cost-effective strategy for orally vaccinating large populations against mucosal infections, including those that may result from an act of bioterrorism. ³⁾

2008 MucoRice: development of rice-based oral vaccine

Review - Nihon Rinsho Meneki Gakkai Kaishi. 2008 Oct;31(5):369-74. doi: 10.2177/jsci.31.369. [MucoRice: development of rice-based oral vaccine] [Article in Japanese] Yoshikazu Yuki 1 , Hiroshi Kiyono

Affiliations PMID: 18974620 DOI: 10.2177/jsci.31.369

Parenteral vaccines are used commonly against most of infectious diseases. It is noted that these injection type vaccines are meant to induce protective immunity in the systemic compartment but not aimed at use of the benefits of mucosal immunity as a first line of defense against mucosal infectious diseases such as AIDS, SARS and Influenza.

In addition, one of major practical obstacles to current vaccination is storage of the vaccine under refrigeration (or cold-chain) in the developing countries. To overcome these concerns, a plant-based vaccine is considered to be an attractive strategy. Currently, we have developed a rice-based oral vaccine that offers significant advantages over available vaccines.

In the rice-based vaccine MucoRice, cholera toxin B subunit (CTB) as the vaccine antigen was accumulated in protein bodies as rice seed storage organella. When orally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches (PPs), and inducing toxin-specific serum IgG and mucosal IgA antibodies with neutralizing activity.

Further, MuocRice CTB remained stable state and maintained immunogenicity at room temperature for 1.5 years and was protected from pepsin digestion in vitro. Taken together, these findings suggest that MucoRice does not require needle/syringe and cold-chain but induces two layers of immunity in both mucosal and systemic compartments, which is the most effective and highly practical global vaccine to combat emerging and re-emerging infectious diseases. ⁴⁾

2021 Rice-based Cholera Vaccine Induces Antibodies in Small Trial

July 8, 2021 Rice-based Cholera Vaccine Induces Antibodies in Small Trial

Immune-response levels to the edible vaccine varied among the subjects, possibly due to differences in the gut microbiome.

by Alejandra Manjarrez

Oral vaccines are currently part of the strategy to control the acute diarrheal disease caused by Vibrio cholera, especially in areas with poor sanitation. Yet, even at less than US $2 per dose, these vaccines can be costly for widespread use by poorer countries, and there remain 1.3–4 million estimated cases of cholera worldwide per year, and about 21,000 to 143,000 deaths from the disease. Now, the results of the first human trial of an edible cholera vaccine made from engineered rice show it increased antibody concentrations against a diarrheal toxin without inducing severe adverse events in the study participants, according to a report published June 25 in The Lancet Microbe.

The idea of using plants as biological vaccine factories is decades old. It’s a beautiful concept, says mucosal immunologist Hiroshi Kiyono of the University of Tokyo, but such vaccines haven’t materialized partly because most plants cannot be preserved for a long time period, which raises the cost of distribution and storage. Kiyono, who led the current work, says he and his colleagues thought that cereals such as rice could potentially overcome that obstacle, as seeds can be stored for a long time without refrigeration.

The idea of using rice to make a heat-stable vaccine is really creative, says Vanessa Harris, an infectious disease specialist at the Amsterdam University Medical Center who did not participate in the study. Furthermore, “it has real significance for low-[to]-middle-income countries,” she says, as its characteristics make it “easy to administer, store, and distribute.”

Kiyono and his colleagues chose to target the cholera toxin, which is responsible for the severe watery diarrhea associated with a cholera infection. They first reported the development of this rice-based vaccine in 2007, showing that genetically engineered seeds successfully expressed the cholera toxin B subunit (CTB) and induced an antigen-specific immune response in vitro. Further studies in mice and macaques confirmed that oral immunization with the vaccine, dubbed MucoRice-CTB, induced high levels of CTB-specific antibodies in the serum of these animal models. ⁵⁾

2022 Mosquitos Genetically Modified To Vaccinate Humans

The Counter Signal by Mike Campbell September 27, 2022

A box full of genetically modified mosquitos successfully vaccinated a human against malaria in a trial funded by the National Institute of Health (NIH).

“We use the mosquitoes like they’re 1,000 small flying syringes,” said researcher Dr. Sean Murphy, as reported by NPR.

Three to five “vaccinations” took place over 30-day intervals.

The mosquitos gave minor versions of malaria that didn’t make people sick, but gave them antibodies. Efficacy from the antibodies lasted a few months.

“Half of the individuals in each vaccine group did not develop detectable P. falciparum infection, and a subset of these individuals was subjected to a second CHMI 6 months later and remained partially protected. These results support further development of genetically attenuated sporozoites as potential malaria vaccines,” researchers concluded.

Carolina Reid was one of twenty-six participants in the study.

“My whole forearm swelled and blistered. My family was laughing, asking like, ‘why are you subjecting yourself to this?'”

Reid enjoyed her experience so much that she says she wants to participate in as many vaccine trials as she can. For this research, each participant received $4,100 as an incentive.

Dr. Kirsten Lyke calls the research “a total game changer.”

Lyke led the phase 1 trials for Pfizer’s COVID-19 vaccine and was a co-investigator for Moderna and Novavax COVID vaccines.

Researchers say the genetically modified mosquitos will not be used at large to vaccinate millions of people. The reason why mosquitos were used instead of syringes, they claim, was to save costs. ⁶⁾