KLH Aquaculture Manufacturing

Highly-specialized aquaculture manufacturing can protect the KLH molecule's source species (Megathura crenulata) and ensure sustainable supply of fully-traceable, quality KLH protein.

Scientists have isolated many useful chemicals from marine organisms but their promise as future drugs or research molecules are often hampered by manufacturing and supply challenges.

KLH protein is derived only from the hemolymph of the Giant Keyhole Limpet (Megathura crenulata), which is native only to the Pacific coastal waters off of portions of California and Baja, Mexico.  Natural habitat for this relatively scarce marine species is the shallow, rocky waters below low tide line.

Aquaculture Provides Sustainability & Traceability

The concept of sustainability involves sound, responsible management of environmental resources and, especially where biological systems are concerned, includes protecting native species so that they thrive and remain diverse and productive over time.

Historically, KLH protein was often obtained by unlicensed suppliers, directly from wild and sensitive populations of Megathura crenulata, and involved lethal production processes.  Attempts at holding limpets in captivity proved problematic for some suppliers, so they obtained limpets from the wild, and held them temporarily for the purposes of hemolymph extraction.

As a result, commercial supplies of KLH have differed widely in their source, traceability, purity, form, and preparation, as well as in immunogenicity.  Studies have demonstrated that source and form of KLH matter (1,2,3).

KLH produced from limpet populations thriving and reproducing in licensed aquaculture (rather than from small and sensitive wild populations) can protect the precious source species Megathura crenulata and ensure long-term, scalable supply of this important biomedical material.  Further, the environmentally sound methods associated with professional and specialized aquaculture have been shown to minimize variability in KLH product (4).

Read Protecting the Sole Marine Source of an Important Pharmaceutical Product

Aquaculture Protects Sensitive Wild Populations

The long-term survival of marine gastropods – the scientific class to which Megathura crenulata belongs – is a global issue.  For example, failure to manage the California abalone (Haliotis spp.) resulted in dramatic declines and eventually led to complete closure of the commercial and recreational fishery (5).  Other examples include observed decreases in nearshore Florida Queen conch, S. gigas, with reproductive alterations (6); and, pollution related changes in Japanese populations of large giant abalone (Haliotis madaka) (7).  Observed environmental levels of phosphonates and sulfonates; organic pollutants including tributyltin and phthalates; heavy metals and copper; and xenoestrogens such as bisphenols have been implicated in reproductive abnormalities in mollusks including prosobranch snails and in archeogastropods such as Haliotis.  Reproductive abnormalities include superfemininization in gastropod males; imposex conversions in mollusk and archeogastropod females; and lethal effects on embryogenesis (6,7,8,9,10,11,12). 

Populations of Megathura crenulata (Giant Keyhole Limpet) are believed to be in decline on the California coast, but recent population studies are lacking.

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(1) Lebrec, Hock, Sundsmo, Mytych, Chow, Carlock, Joubert. T-cell Dependent Antibody Responses in the rat: Forms and sources of keyhole limpet hemocyanin matter. Poster presentation, Annual Meeting of the Society of Toxicology (SOT) 2013.
(2) Herscowitz, Harold, and Stavitsky. Immunochemical and immunogenic properties of a purified keyhole limpet haemocyanin. Immunol. 1972; 22: 51-61.
(3) Miller, Curtsinger, Berthold, Malvey, Bliss, Le, Fautsch, Dudek, Blazar and Panoskaltsis-Mortari. Diminished neo-antigen response to keyhole limpet hemocyanin (KLH) vaccines in patients after treatment with chemotherapy or hematopoietic cell transplantation. Clin. Immunol. 2005;117: 144-151.
(4) Oakes FR, McTee S, McMullen J, Culver CS, Morse, DE. The effect of captivity and diet on KLH isoform ratios in Megathura crenulata. Comp Biocehm and Phys. Part A 138 (2004): 169-173.
(5) Karpov KA, Haaker PL, Taniguchi IK, Rogers-Bennett L. Serial depletion and the collapse of the California abalone (Haliotis spp.) fishery.In Workshop on Rebuilding Abalone Stocks in British Columbia. Edited by A.Campbell. Can. Spec. Publ. Fish. Aquat. Sci.130 pp11-24.
(6) Spade DJ, Griffitt RJ, Liu L, Brown-Peterson NJ, Kroll KJ, Feswick A, Glazer RA, Barber DS, Denslow ND. 2010. Queen conch (Strombus gigas) testis regresses during the reproductive season at nearshore sites in the Florida Keys. PLoS One. Sep 15;5(9):e12737.
(7) Horiguchi T, Kojima M, Takiguchi N, Kaya M, Shiraishi H, Morita M. 2005. Continuing observation of disturbed reproductive cycle and ovarian spermatogenesis in the giant abalone, Haliotis madaka from an organotin-contaminated site of Japan. Mar Pollut Bull. 2005;51(8-12):817-22.
(8) Zhou J, Zhu XS, Cai ZH. 2011. The impacts of bisphenol A (BPA) on abalone (Haliotis diversicolor supertexta)embryonic development. Chemosphere. Jan;82(3):443-50.
(9) Ducrot V, Teixeira-Alves M, Lopes C, Delignette-Muller ML, Charles S, Lagadic L. 2010. Development of partial life-cycle experiments to assess the effects of endocrine disruptors on the freshwater gastropod Lymnaea stagnalis: a case-study with vinclozolin. Ecotoxicology. Oct;19(7):1312-21.
(10) Sternberg RM, Gooding MP, Hotchkiss AK, LeBlanc GA. 2010. Environmental-endocrine control of reproductive maturation in gastropods:implications for the mechanism of tributyltin-induced imposex in prosobranchs. Ecotoxicology. Jan;19(1):4-23.
(11) Liu Y, Guan Y, Yang Z, Cai Z, Mizuno T, Tsuno H, Zhu W, Zhang X. 2009. Toxicity of seven phthalate esters to embryonic development of the abalone Haliotis diversicolor supertexta. Ecotoxicology. Apr;18(3):293-303.
(12) Horiguchi T, Kojima M, Kaya M, Matsuo T, Shiraishi H, Morita M, Adachi Y. 2002. Tributyltin and triphenyltin induce spermatogenesis in ovary of female abalone,Haliotis gigantea. Mar Environ Res. 2002 Sep-Dec;54(3-5):679-84.