Ishizuka Andrew S, Lyke Kirsten E, DeZure Adam, Berry Andrea A, Richie Thomas L, Mendoza Floreliz H, Enama Mary E, Gordon Ingelise J, Chang Lee-Jah, Sarwar Uzma N, Zephir Kathryn L, Holman LaSonji A, James Eric R, Billingsley Peter F, Gunasekera Anusha, Chakravarty Sumana, Manoj Anita, Li MingLin, Ruben Adam J, Li Tao, Eappen Abraham G, Stafford Richard E, K C Natasha, Murshedkar Tooba, DeCederfelt Hope, Plummer Sarah H, Hendel Cynthia S, Novik Laura, Costner Pamela J M, Saunders Jamie G, Laurens Matthew B, Plowe Christopher V, Flynn Barbara, Whalen William R, Todd J P, Noor Jay, Rao Srinivas, Sierra-Davidson Kailan, Lynn Geoffrey M, Epstein Judith E, Kemp Margaret A, Fahle Gary A, Mikolajczak Sebastian A, Fishbaugher Matthew, Sack Brandon K, Kappe Stefan H I, Davidson Silas A, Garver Lindsey S, Björkström Niklas K, Nason Martha C, Graham Barney S, Roederer Mario, Sim B Kim Lee, Hoffman Stephen L, Ledgerwood Julie E, Seder Robert A
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
Institute for Global Health, Center for Vaccine Development and Division of Malaria Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Nat Med. 2016 Jun;22(6):614-23. doi: 10.1038/nm.4110. Epub 2016 May 9.
An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.7 × 10(5) PfSPZ, 6/11 (55%) vaccinated subjects remained without parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic subjects from this dosage group underwent repeat CHMI at 59 weeks, and none developed parasitemia. Although Pf-specific serum antibody levels correlated with protection up to 21-25 weeks after immunization, antibody levels waned substantially by 59 weeks. Pf-specific T cell responses also declined in blood by 59 weeks. To determine whether T cell responses in blood reflected responses in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific interferon-γ-producing CD8 T cells were present at ∼100-fold higher frequencies in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection.
一种减毒恶性疟原虫（Pf）子孢子（SPZ）疫苗，即PfSPZ疫苗，在免疫后3周对受控人体疟疾感染（CHMI）具有高度保护作用，但保护的持久性尚不清楚。我们评估了疫苗剂量、接种方案和给药途径如何影响未感染疟疾的成年人的持久保护作用。在用2.7×10⁵个PfSPZ进行四次静脉免疫后，11名接种疫苗的受试者中有6名（55%）在免疫后21周的CHMI后仍无寄生虫血症。该剂量组的5名无寄生虫血症的受试者在59周时接受了重复CHMI，无一例出现寄生虫血症。尽管Pf特异性血清抗体水平在免疫后长达21 - 25周与保护作用相关，但到59周时抗体水平大幅下降。到59周时，血液中的Pf特异性T细胞反应也有所下降。为了确定血液中的T细胞反应是否反映了肝脏中的反应，我们用PfSPZ疫苗对非人灵长类动物进行了接种。Pf特异性产生干扰素-γ的CD8 T细胞在肝脏中的频率比在血液中高约100倍。我们的研究结果表明，PfSPZ疫苗通过长寿的组织驻留T细胞对疟疾赋予了持久保护作用，并且给予更高剂量可能会进一步增强保护作用。
