key: cord-0697480-mzdou0sb
authors: Macdonald, Catherine; Soll, Joshua
title: Shark conservation risks associated with the use of shark liver oil in SARS-CoV-2 vaccine development
date: 2020-10-15
journal: bioRxiv
DOI: 10.1101/2020.10.14.338053
sha: 86b4524c15d8db344324b4504854c874654ed1af
doc_id: 697480
cord_uid: mzdou0sb

The COVID-19 pandemic may create new demand for wildlife-generated products for human health, including a shark-derived ingredient used in some vaccines. Adjuvants are a vaccine component that increases efficacy, and some adjuvants contain squalene, a natural compound derived from shark liver oil which is found most abundantly in deep-sea sharks. In recent decades, there has been growing conservation concern associated with the sustainability of many shark fisheries. The need for a potentially massive number of adjuvant-containing SARS-CoV-2 vaccines may increase global demand for shark-derived squalene, with possible consequences for shark conservation, especially of vulnerable and understudied deep-sea species. A shift to non-animal-derived sources of squalene, which are similar in cost and identical in effectiveness, or an emphasis on increasing traceability and sustainability of shark-derived squalene from existing well-managed fisheries, could better support conservation and public health goals.

Sinan, 2014). Sharks, particularly deep-sea species, tend to grow slowly and produce relatively 35 few young, leaving them especially susceptible to overexploitation (Simpfendorfer and Kyne, 36 2009). Squalene is a natural polyunsaturated hydrocarbon compound (C₃₀H₅₀) found in many 37 living organisms that can be refined from shark liver oil. This compound (and its more stable, 38 hydrogenated derivate, squalane) have shown genuine potential to contribute to human health, as 39 an ingredient in vaccines and other pharmaceuticals and dietary supplements (Kim and 40

Karadeniz, 2012). 41 42

Many shark species, particularly deep-sea sharks, have relatively large livers (up to 20% of 43 animal weight) which serve as a buoyancy control system and critical energy reserve 44 (Vannuccini 1999 ; Abel and Grubbs 2020). A significant portion of liver weight is made up of 45 liver oil (10-70%; Nichols et al., 2001) , and between 15 and 82% of liver oil is squalene (Deprez 46 et al., 1990; Bakes & Nichols 1995) . Although squalene is produced by a range of animals and 47 plants, shark liver oil has historically been a preferred commercial source based on availability 48 and high yields relative to most plant-derived sources. 49 50

Squalene can be extracted directly from shark liver oil at high purity (>98%) in approximately 10 51 hours, using a single distillation process in a vacuum at 200-230º C, a faster process producing 52 greater yields than plant-based alternatives (Camin et al., 2010) . Sealed and protected from 53 oxygen and light, squalene has an approximately two-year shelf life, making stable rates of 54 ongoing production important to availability (Camin et al., 2010). Plant-derived squalene can 55 also be refined to a high level of purity for medical applications, and is made up of C₃₀H₅₀ 56 molecules chemically identical to those from shark-derived sources. Plant-derived squalene has 57 been shown to perform comparably to shark-derived squalene as an ingredient in vaccine 58

adjuvants (Brito et al. 2011 The global trade in shark liver oil is small compared to that in shark fins or meat, and despite the 137 vulnerability of some target species to overfishing has received relatively little media (Shiffman 138 et al., 2020) or scientific attention (Dent and Clarke, 2015). Although there are fisheries in which 139

deep-sea sharks are targeted (see, e.g., Simpfendorfer and Kyne, 2007) , liver oil may also be 140 generated opportunistically from incidental catches in fisheries predominantly targeting other 141 fish, or targeting sharks for other products (e.g., meat, fins). In at least some cases, however, the 142 export value of shark liver oil exceeds that of shark meat, and in some locales the available 143 supply of shark liver oil is insufficient to meet processors' demand for raw materials (Dent and  144 Clarke, 2015). A lack of traceability presents a further challenge in assessing the trade in shark 145 liver oil, as the United Nations Food and Agriculture Organization (FAO)'s Codex Alimentarius 146 allows for products like squalene to be labelled as originating in the countries in which they were 147 processed even when ingredients (e.g., the liver oil from which the squalene was derived) were 148 produced elsewhere (FAO, 2001) . 149 150

This study provides a basis for beginning to evaluate the range of potential conservation effects 151 of increasing demand for shark-derived squalene as an ingredient in vaccine adjuvants. 152 153

2. Materials and methods 154 155

Based on a review of available scientific and management literature, 133 species were identified 156 which are known to be involved in the liver oil trade (Appendix 1), including many that are 157 partially reliant on deep-sea habitat >200 m (n=83) or are found exclusively in the deep-sea 158 (n=21). Additional data on the conservation status and population trends of elasmobranch 159 species, primarily sharks, identified as being involved in the liver oil trade were compiled from 160 their most recent IUCN Red List assessments. Available current trade data on the shark liver oil 161 trade was downloaded from the UN FAO FishStat Database (FAO, 2020). Commercial sources 162 of wholesale quantities of squalene were identified through internet searches and through direct 163 contact with wholesalers to collect pricing, origin, and availability information for both plant-164 and shark-derived squalene and squalane (its more stable, hydrogenated derivate). 165 166

3. Results 167 168

Across elasmobranch species identified as being exploited for shark liver oil, 50% had not been 169 assessed by the IUCN in at least ten years, and 30% were considered Data Deficient ( estimate (for yield assumptions see Table 1 ). 186 187

Data collected on the price of shark-and plant-derived squalene showed no clear differences, 188 though products listed as both shark-and plant-derived were commonly available in the 189 wholesale market ( These results highlight the extent to which liver oil fisheries could affect shark species of 207 conservation concern, and the potential difficulty of detecting these effects because of a lack of 208 information on the volume of liver-oil-associated catch and the absence of population status We know that fisheries primarily targeting sharks for liver oil exist (e.g., Kyne and 225 Simpfendorfer, 2007) , and that, in many cases, multiple products may be marketed from a single 226

shark (e.g., meat, fins, liver oil, cartilage). Data are not available to assess the volume of liver oil 227 generated globally by directed versus incidental fishing. The effect of increased demand for 228 shark-derived squalene is highly dependent on whether it increases targeting of oil-rich deep-sea 229

sharks, or simply drives increased processing and use of the livers of sharks currently taken for 230 other purposes. Oceana EU. https://eu.oceana.org/en/press-center/press-releases/consumers-unaware-329 endangered-shark-liver-oil-cosmetics (accessed 28 Aug 2020). 330 COVID-19 Could Become..., 2020. COVID-19 Could Become a Seasonal Illness: What We'll 331

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Enhanced Passive 408 Safety Surveillance (EPSS) confirms an optimal safety profile of the use of MF59®-adjuvanted 409 influenza vaccine in older adults: Results from three consecutive seasons. Influenza Other 410 Respiratory Viruses

Analysis of fin and non-fin fish 412 products for azamethiphos and dichlorvos residues from the Canadian retail market

Squalene-containing licensed adjuvants enhance 417 strain-specific antibody responses against the influenza hemagglutinin and induce subtype-418 specific antibodies against the neuraminidase

Safety of MF59(TM) 421 adjuvant

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Optimization of squalene extraction from Palm Fatty 430

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SARS Vaccine Protective in Mice. Emerging 437 Infectious Diseases

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Appendix A: Elasmobranchs reported to be used in the liver oil and squalene trades, including 504 IUCN conservation status and population trend assessment information. 505 506