INSIGHTS | P E R S P E C T I V E S

nationalizing Iran’s uranium enrichment program could become a step toward phasing out or multinationalizing national enrichment programs worldwide as part of a regime in which nuclear power rules apply equally to all states. Uranium enrichment is required by the “light” (ordinary) water-cooled reactors that dominate the current global nuclear power reactor fleet. National enrichment programs currently exist in China, France, and Russia. None of these states has enriched uranium for weapon purposes since the end of the Cold War. India, Pakistan, and North Korea enrich uranium on a much smaller scale, including for military purposes. Three nonweapon states also have national enrichment plants: Japan, Brazil, and Iran. An alternative to national enrichment plants emerged in the 1970s in the form of Urenco, a company jointly controlled by Germany, the Netherlands, and the United Kingdom, which operates one enrichment plant in each of these countries. Urenco currently operates 60% of the enrichment capacity outside Russia and owns the only commercial enrichment facility currently operating in the United States. This plant supplies about 40% of U.S. requirements, with the remainder imported. Most countries with nuclear power plants purchase uranium enrichment services from Urenco and Russia. Since 1983, the United States has argued with countries interested in launching spentfuel reprocessing (plutonium-separation) programs, in effect, “We don’t reprocess. You don’t need to either.” This argument, reinforced by the poor economics of plutonium recycling, helped discourage additional countries from launching reprocessing programs. The United States is now in a position to argue similarly with countries like Iran, “We have the largest nuclear power program in the world, but we currently don’t have a national enrichment program. You don’t need one either.” By committing, as part of the forthcoming deal on Iran’s nuclear program, to working on multinational enrichment arrangements for the Middle East, and ultimately around the world, Iran and the E3+3 could chart a path to reduce the proliferation risks from 1322

REFERENCES AND NOTES

1. Joint Statement by EU High Representative Federica Mogherini and Iranian Foreign Minister Javad Zarif Switzerland, 2 April 2015; http://eeas.europa.eu/ statements-eeas/2015/150402_03_en.htm. 2. The United States issued a fact sheet on the same day detailing its view of the obligations agreed to in April 2015, “Parameters for a Joint Comprehensive Plan of Action regarding the Islamic Republic of Iran’s Nuclear Program”; www.whitehouse.gov/sites/default/files/docs/parametersforajointcomprehenisveplanofaction.pdf. 3. Treaty on the Non-Proliferation of Nuclear Weapons (NPT), United Nations Office of Disarmament Affairs (1968); www.un.org/disarmament/WMD/Nuclear/ NPTtext.shtml, Article IV. 4. International Atomic Energy Agency (IAEA), “Communication Dated 27 November 2013 Received From the EU High Representative to the Agency Concerning the Text of the Joint Plan of Action,” INFCIRC/855, 27 November 2013; www.iaea.org/sites/ default/files/publications/documents/infcircs/2013/ infcirc855.pdf. 5. D. E. Sanger, “Saudi Arabia Promises to Match Iran in Nuclear Capability,” New York Times, 13 May 2015. 6. U.S. State Department, A Report on the International Control of Atomic Energy (1946); www.fissilematerials. org/library/ach46.pdf 7. A. Glaser, Internationalization of the Nuclear Fuel Cycle, International Commission on Nuclear Non-proliferation and Disarmament, ICNND Research Paper No. 9 (February 2009). 8. The Tehran Research Reactor was provided to Iran by the United States in 1960. It was fueled with weapon-grade uranium fuel. Argentina converted it to 19.75% enriched uranium fuel in 1992. IAEA, Research Reactor Database, nucleus.iaea.org/RRDB/RR/ReactorSearch.aspx. 9. This includes production losses, IAEA, Safeguards Glossary, 2001 edition (International Atomic Energy Agency, Vienna, 2002), p. 23. 10. D. Albright, S. Kelleher-Vergantini, A. Stricker, P. Izewicz, D. Schnur, ISIS Analysis of IAEA Iran Safeguards Report (Institute for Science and International Security, Washington, DC, 19 February 2015). 11. It has been assumed that the associated depleted uranium produced contains 0.4% U-235, as has been Iran’s practice. 12. Organization of Atomic Energy of Iran, “Bushehr Power Plant Fuel Reserve was replaced,” 11 March 2014; www. aeoi.org.ir. 13. Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC), www.abacc.org.br. 14. The states are Algeria, Bahrain, Comoros, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Mauritania, Morocco, Oman, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Tunisia, United Arab Emirates, and Yemen. Note by the Secretary-General regarding letter received from member states confirming support for declaring the Middle East a region free from weapons of mass destruction, including nuclear, chemical, and biological weapons, 6 March 2014; www.un.org/disarmament/WMD/ menbcletters. 15. F. N. von Hippel, S. Hossein Mousavian, E. Kiyaei, H. A. Feiveson, Z. Mian, “Fissile Material Controls in the Middle East: Steps toward a Middle East Zone Free of Nuclear Weapons and all other Weapons of Mass Destruction,” International Panel on Fissile Materials, October 2013; www.fissilematerials.org/library/rr11.pdf

IMMUNOLOGY

A Chlamydia vaccine on the horizon Results of a new Chlamydia vaccine in mice should spur human clinical trials By Robert C. Brunham

C

hlamydia trachomatis is the most common reported sexually transmitted bacterial infection in the United States, with more than 1.4 million cases of infection reported to the U.S. Centers for Disease Control and Prevention in 2012 (1). Worldwide, it is likely the most common infectious cause of infertility in women. An estimated 106 million cases of C. trachomatis occur globally among both women and men each year, so the worldwide burden of disease is substantial. Current public health efforts to prevent sexually transmitted disease caused by C. trachomatis or Neisseria gonorrhoeae emphasize prevention, but screening and treatment programs in medium- and lowincome countries are rarely implemented because of financial and logistical difficulties. The findings reported by Stary et al. on page 1331 of this issue (2) constitute a major step forward in understanding C. tracho-

ACKNOWLEDGMENTS

We thank anonymous reviewers for comments. SUPPLEMENTARY MATERIALS

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Ready to spread. A colored scanning electron micrograph of a human cervix cancer cell infected with C. trachomatis is shown. At the center is an inclusion body (ripped open) containing hundreds of Chlamydia particles. sciencemag.org SCIENCE

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MULTINATIONAL ENRICHMENT. Multi-

national control of civilian enrichment plants, regardless of location. In parallel, a Fissile Material Cutoff Treaty would end unsafeguarded uranium enrichment in the weapon states. ■

PHOTO: SPL/SCIENCE SOURCE

Secretary General confirming support for declaring the Middle East a region free from WMDs (14). Achieving a Middle East nuclear weapon–free zone, as part of a Middle East WMD-free zone, would benefit from all its members accepting the enrichment and reprocessing restrictions and enhanced transparency obligations agreed to by Iran and eventually will require Israel to verifiably give up its nuclear weapons (15).

ILLUSTRATION: C. BICKEL/SCIENCE

matis immunobiology and could carrier adjuvant incorporating translate into a vaccine that galthe drug resiquimod was used to vanizes mucosal T cells against aggregate inactivated C. trachothis pathogen. matis cells as a vaccine (resiquiFallopian tube C. trachomatis is a Grammod is an agonist of Toll-like infection negative bacterium that infects receptor 7 expressed in immune both men and women. It is taken and nonimmune cells that detect up by mucosal epithelial cells, pathogens and elicit immune Ovary replicates within a vacuole, and responses). Within the mucosal within 48 hours, bacteria are reenvironment, UV-inactivated C. leased to infect neighboring cells trachomatis, in the presence or (see the first figure). It can cause absence of the nanocarrier adserious, permanent damage to a juvant, differentially recruited Uterus woman’s reproductive system, CD103-negative or -positive denand a pregnant woman can pass dritic cells, which in turn actian infection to her baby during vated CD4 TH1 cells or CD4 Treg Fallopian tube delivery. It can also cause blindcells, respectively. Protective CD4 obstruction ness. Even if treated for a past C. TH1 cells homed to the mucosa trachomatis infection with antivia an adhesion (integrin)–debiotics, one can still get infected pendent mechanism. CD4 Treg again through unprotected sex. cells correlated with enhanced About 15% of untreated chlamydinfection. ial infections lead to pelvic inParticularly elegant parabioflammatory disease, a condition sis experiments (joining the cirof public health concern because culatory systems of two mice) Cervical it can lead to infertility, ectopic allowed Stary et al. to assess infection pregnancy, and chronic pelvic the movement and function of pain (3) (see the second figure). traceable C. trachomatis–specific Pelvic infammatory Many high-income countries CD4 T cells. The authors demondisease have implemented programs to strated that two waves of protecVaginal screen and treat women for astive CD4 TH1 cells develop after canal ymptomatic C. trachomatis infecmucosal immunization with the tion (most infected individuals UV-inactivated C. trachomatis– have no symptoms, or symptoms nanocarrier adjuvant vaccine. may not appear until several Reproductive damage. Pelvic inflammatory disease in women caused by C. The first wave generated mucoweeks after sex with an infected trachomatis (sites of infection shown) can result in tubal factor infertility, ectopic sal resident T cells that provided partner). These efforts are based pregnancy, and chronic pelvic pain. early protection, and a second on evidence from randomized wave generated systemic T cells controlled trials indicating that screening The experiments reported by Stary et al. that augmented early and late protection. for and treating cervical C. trachomatis inprovide a mechanistic explanation for earAlthough mucosal immunization with adjufection can reduce a woman’s risk of pelvic lier clinical and experimental findings. Durvant induced both waves of T cells, systemic inflammatory disease by approximately 30 ing the 1960s, human chlamydia vaccine immunization induced only the second wave to 50% over 1 year. Since the introduction trials in low- and medium-income countries and manifested incomplete protection. Thus, of these public health programs, pelvic inshowed that inactivated whole C. trachomaearly recruitment of mucosal CD4 TH1 cells is flammatory disease rates have fallen dratis vaccines (given with either an oil/water likely key to a successful C. trachomatis vacmatically in developed countries. However, or alum adjuvant) protected against C. tracine. The density of mucosal CD4 TH1 cells is control has been incomplete because of chomatis ocular disease (trachoma) in most a known correlate of immunity for this oblilimitations in uptake, cost, and unexpected subjects, but waned after 1 year (4). Examigate intracellular epithelial cell pathogen (6). increases in infection incidence. nation of vaccinated nonhuman primates A vaccine to prevent sexually transmitThe situation is worse in the developing also showed that breakthrough secondary ted C. trachomatis infection would advance world. Tubal factor infertility is the major infections could occur with even worse papublic health efforts to control this prevalent sequela of untreated C. trachomatis pelvic thology (5). These studies showed that inacsexually transmitted disease. Translating inflammatory disease and may be present tivated bacteria could induce a protective these findings into human C. trachomatis in 65 to 85% of women who seek infertilresponse, albeit a subimmunogenic one. vaccine trials would bring us closer to this ity care in sub-Saharan Africa. The World Stary et al. demonstrate that mucosal imgoal and spur the development of vaccines Health Organization has concluded that munization of mice (either intrauterine or for other mucosal pathogens. ■ the development of a vaccine against C. intranasal application) with ultraviolet light REFERENCES trachomatis is a priority for the preven(UV)–inactivated C. trachomatis can elicit 1. K. Owusu-Edusei et al., Emerg. Infect. Dis. 21, 960 (2015). tion of pelvic inflammatory disease and its either protective CD4 T helper (TH1) cells 2. G. Stary et al., Science 348, aaa8205 (2015). long-term sequelae. or CD4 T regulatory (Treg) cells that tolerate 3. R. C. Brunham et al., N. Engl. J. Med. 372, 2039 (2015). 4. D. C. Mabey et al., Vaccine 32, 1572 (2014). infection, depending on the adjuvant cho5. J. T. Grayston, S. Wang, J. Infect. Dis. 132, 87 (1975). sen. TH1 cells function in long-term protec6. J. U. Igietseme, R. G. Rank, Infect. Immun. 59, 1346 (1991). Department of Medicine, University of British Columbia, tive memory after infection. A cationically Vancouver, BC V6X 1N4, Canada. charged synthetic and biodegradable nano10.1126/science.aac6528 E-mail: [email protected] SCIENCE sciencemag.org

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A Chlamydia vaccine on the horizon Robert C. Brunham Science 348, 1322 (2015); DOI: 10.1126/science.aac6528

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