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David R. Martinez, PhD

Assistant Professor; Affiliated Faculty, Yale Institute for Global Health

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David R. Martinez, PhD

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Research Summary

I study immunity to viral pathogens of global importance including coronaviruses, flaviviruses, and other emerging viruses. The laboratory of Viral Pathobiology and Immunity (Martinez lab) studies interactions between viral entry proteins and host antibody responses with the goal of informing universal and broad-based vaccine approaches. In this line of work, we have defined broadly conserved targets in SARS-related viruses that share epitopes with SARS-CoV and SARS-CoV-2. Based on these studies we are developing universal vaccination strategies that harness these broadly conserved epitopes in pandemic coronaviruses and these vaccines can protect animals from disease. In addition, we are interested in defining how antibodies protect or enhance disease against flaviviruses including Dengue virus, Zika virus, West Nile virus, Yellow Fever virus, and other emerging flaviviruses. Our studies on coronavirus and flavivirus interactions with host antibodies are being used to design rational vaccination strategies against these emerging viruses which are a major threat to global public health.

Research Interests

Arboviruses; Flavivirus; Infections; Inflammation; RNA Viruses; Virology; Coronavirus; Flavivirus Infections; Immunity, Mucosal; Dengue Vaccines

Public Health Interests

Global Health; Immunology; Infectious Diseases; Respiratory Disease/Infections; Vaccines; Viruses; Zoonotic Diseases; Neglected Tropical Diseases; Mosquito-borne Diseases; Vector-borne Diseases; COVID-19

Selected Publications

  • Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.Martinez DR, Schäfer A, Leist SR, De la Cruz G, West A, Atochina-Vasserman EN, Lindesmith LC, Pardi N, Parks R, Barr M, Li D, Yount B, Saunders KO, Weissman D, Haynes BF, Montgomery SA, Baric RS. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science 2021, 373: 991-998. PMID: 34214046, DOI: 10.1126/science.abi4506.
  • Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women.Martinez DR, Fong Y, Li SH, Yang F, Jennewein MF, Weiner JA, Harrell EA, Mangold JF, Goswami R, Seage GR 3rd, Alter G, Ackerman ME, Peng X, Fouda GG, Permar SR. Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women. Cell 2019, 178: 190-201.e11. PMID: 31204101, DOI: 10.1016/j.cell.2019.05.046.
  • Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice.Martinez DR, Schäfer A, Gavitt TD, Mallory ML, Lee E, Catanzaro NJ, Chen H, Gully K, Scobey T, Korategere P, Brown A, Smith L, Parks R, Barr M, Newman A, Bowman C, Powers JM, Soderblom EJ, Mansouri K, Edwards RJ, Baric RS, Haynes BF, Saunders KO. Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice. Cell Rep 2023, 113248. PMID: 37858337, DOI: 10.1016/j.celrep.2023.113248.
  • Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine.Li D, Martinez DR, Schäfer A, Chen H, Barr M, Sutherland LL, Lee E, Parks R, Mielke D, Edwards W, Newman A, Bock KW, Minai M, Nagata BM, Gagne M, Douek DC, DeMarco CT, Denny TN, Oguin TH 3rd, Brown A, Rountree W, Wang Y, Mansouri K, Edwards RJ, Ferrari G, Sempowski GD, Eaton A, Tang J, Cain DW, Santra S, Pardi N, Weissman D, Tomai MA, Fox CB, Moore IN, Andersen H, Lewis MG, Golding H, Seder R, Khurana S, Baric RS, Montefiori DC, Saunders KO, Haynes BF. Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine. Nat Commun 2022, 13: 6309. PMID: 36274085, DOI: 10.1038/s41467-022-33985-4.
  • Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice.Schäfer A, Martinez DR, Won JJ, Meganck RM, Moreira FR, Brown AJ, Gully KL, Zweigart MR, Conrad WS, May SR, Dong S, Kalla R, Chun K, Du Pont V, Babusis D, Tang J, Murakami E, Subramanian R, Barrett KT, Bleier BJ, Bannister R, Feng JY, Bilello JP, Cihlar T, Mackman RL, Montgomery SA, Baric RS, Sheahan TP. Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice. Sci Transl Med 2022, 14: eabm3410. PMID: 35315683, DOI: 10.1126/scitranslmed.abm3410.
  • A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.Martinez DR, Schäfer A, Gobeil S, Li D, De la Cruz G, Parks R, Lu X, Barr M, Stalls V, Janowska K, Beaudoin E, Manne K, Mansouri K, Edwards RJ, Cronin K, Yount B, Anasti K, Montgomery SA, Tang J, Golding H, Shen S, Zhou T, Kwong PD, Graham BS, Mascola JR, Montefiori DC, Alam SM, Sempowski G, Sempowski GD, Khurana S, Wiehe K, Saunders KO, Acharya P, Haynes BF, Baric RS. A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice. Sci Transl Med 2022, 14: eabj7125. PMID: 34726473, DOI: 10.1126/scitranslmed.abj7125.
  • Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines.Collier AY, Yu J, McMahan K, Liu J, Chandrashekar A, Maron JS, Atyeo C, Martinez DR, Ansel JL, Aguayo R, Rowe M, Jacob-Dolan C, Sellers D, Barrett J, Ahmad K, Anioke T, VanWyk H, Gardner S, Powers O, Bondzie EA, Wan H, Baric RS, Alter G, Hacker MR, Barouch DH. Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines. N Engl J Med 2021, 385: 2010-2012. PMID: 34648703, DOI: 10.1056/NEJMc2115596.
  • In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.Li D, Edwards RJ, Manne K, Martinez DR, Schäfer A, Alam SM, Wiehe K, Lu X, Parks R, Sutherland LL, Oguin TH 3rd, McDanal C, Perez LG, Mansouri K, Gobeil SMC, Janowska K, Stalls V, Kopp M, Cai F, Lee E, Foulger A, Hernandez GE, Sanzone A, Tilahun K, Jiang C, Tse LV, Bock KW, Minai M, Nagata BM, Cronin K, Gee-Lai V, Deyton M, Barr M, Von Holle T, Macintyre AN, Stover E, Feldman J, Hauser BM, Caradonna TM, Scobey TD, Rountree W, Wang Y, Moody MA, Cain DW, DeMarco CT, Denny TN, Woods CW, Petzold EW, Schmidt AG, Teng IT, Zhou T, Kwong PD, Mascola JR, Graham BS, Moore IN, Seder R, Andersen H, Lewis MG, Montefiori DC, Sempowski GD, Baric RS, Acharya P, Haynes BF, Saunders KO. In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies. Cell 2021, 184: 4203-4219.e32. PMID: 34242577, DOI: 10.1016/j.cell.2021.06.021.
  • Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans.Alter G, Yu J, Liu J, Chandrashekar A, Borducchi EN, Tostanoski LH, McMahan K, Jacob-Dolan C, Martinez DR, Chang A, Anioke T, Lifton M, Nkolola J, Stephenson KE, Atyeo C, Shin S, Fields P, Kaplan I, Robins H, Amanat F, Krammer F, Baric RS, Le Gars M, Sadoff J, de Groot AM, Heerwegh D, Struyf F, Douoguih M, van Hoof J, Schuitemaker H, Barouch DH. Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature 2021, 596: 268-272. PMID: 34107529, DOI: 10.1038/s41586-021-03681-2.
  • Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice.Martinez DR, Schäfer A, Leist SR, Li D, Gully K, Yount B, Feng JY, Bunyan E, Porter DP, Cihlar T, Montgomery SA, Haynes BF, Baric RS, Nussenzweig MC, Sheahan TP. Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice. Cell Rep 2021, 36: 109450. PMID: 34289384, DOI: 10.1016/j.celrep.2021.109450.
  • Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, Edwards RJ, Gobeil S, Barr M, Mansouri K, Alam SM, Sutherland LL, Cai F, Sanzone AM, Berry M, Manne K, Bock KW, Minai M, Nagata BM, Kapingidza AB, Azoitei M, Tse LV, Scobey TD, Spreng RL, Rountree RW, DeMarco CT, Denny TN, Woods CW, Petzold EW, Tang J, Oguin TH 3rd, Sempowski GD, Gagne M, Douek DC, Tomai MA, Fox CB, Seder R, Wiehe K, Weissman D, Pardi N, Golding H, Khurana S, Acharya P, Andersen H, Lewis MG, Moore IN, Montefiori DC, Baric RS, Haynes BF. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature 2021, 594: 553-559. PMID: 33971664, DOI: 10.1038/s41586-021-03594-0.
  • The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.Jones BE, Brown-Augsburger PL, Corbett KS, Westendorf K, Davies J, Cujec TP, Wiethoff CM, Blackbourne JL, Heinz BA, Foster D, Higgs RE, Balasubramaniam D, Wang L, Zhang Y, Yang ES, Bidshahri R, Kraft L, Hwang Y, Žentelis S, Jepson KR, Goya R, Smith MA, Collins DW, Hinshaw SJ, Tycho SA, Pellacani D, Xiang P, Muthuraman K, Sobhanifar S, Piper MH, Triana FJ, Hendle J, Pustilnik A, Adams AC, Berens SJ, Baric RS, Martinez DR, Cross RW, Geisbert TW, Borisevich V, Abiona O, Belli HM, de Vries M, Mohamed A, Dittmann M, Samanovic MI, Mulligan MJ, Goldsmith JA, Hsieh CL, Johnson NV, Wrapp D, McLellan JS, Barnhart BC, Graham BS, Mascola JR, Hansen CL, Falconer E. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med 2021, 13 PMID: 33820835, DOI: 10.1126/scitranslmed.abf1906.
  • Dengue Vaccines: The Promise and Pitfalls of Antibody-Mediated Protection.Martinez DR, Metz SW, Baric RS. Dengue Vaccines: The Promise and Pitfalls of Antibody-Mediated Protection. Cell Host Microbe 2021, 29: 13-22. PMID: 33444553, DOI: 10.1016/j.chom.2020.12.011.
  • Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott AB, Flach B, Lin BC, Doria-Rose NA, O'Dell S, Schmidt SD, Corbett KS, Swanson PA 2nd, Padilla M, Neuzil KM, Bennett H, Leav B, Makowski M, Albert J, Cross K, Edara VV, Floyd K, Suthar MS, Martinez DR, Baric R, Buchanan W, Luke CJ, Phadke VK, Rostad CA, Ledgerwood JE, Graham BS, Beigel JH, mRNA-1273 Study Group. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J Med 2020, 383: 2427-2438. PMID: 32991794, DOI: 10.1056/NEJMoa2028436.
  • Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.Corbett KS, Flynn B, Foulds KE, Francica JR, Boyoglu-Barnum S, Werner AP, Flach B, O'Connell S, Bock KW, Minai M, Nagata BM, Andersen H, Martinez DR, Noe AT, Douek N, Donaldson MM, Nji NN, Alvarado GS, Edwards DK, Flebbe DR, Lamb E, Doria-Rose NA, Lin BC, Louder MK, O'Dell S, Schmidt SD, Phung E, Chang LA, Yap C, Todd JM, Pessaint L, Van Ry A, Browne S, Greenhouse J, Putman-Taylor T, Strasbaugh A, Campbell TA, Cook A, Dodson A, Steingrebe K, Shi W, Zhang Y, Abiona OM, Wang L, Pegu A, Yang ES, Leung K, Zhou T, Teng IT, Widge A, Gordon I, Novik L, Gillespie RA, Loomis RJ, Moliva JI, Stewart-Jones G, Himansu S, Kong WP, Nason MC, Morabito KM, Ruckwardt TJ, Ledgerwood JE, Gaudinski MR, Kwong PD, Mascola JR, Carfi A, Lewis MG, Baric RS, McDermott A, Moore IN, Sullivan NJ, Roederer M, Seder RA, Graham BS. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N Engl J Med 2020, 383: 1544-1555. PMID: 32722908, DOI: 10.1056/NEJMoa2024671.
  • Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees.Martinez DR, Yount B, Nivarthi U, Munt JE, Delacruz MJ, Whitehead SS, Durbin AP, de Silva AM, Baric RS. Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees. Cell Rep 2020, 33: 108226. PMID: 33027653, DOI: 10.1016/j.celrep.2020.108226.
  • SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness.Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, Himansu S, Schäfer A, Ziwawo CT, DiPiazza AT, Dinnon KH, Elbashir SM, Shaw CA, Woods A, Fritch EJ, Martinez DR, Bock KW, Minai M, Nagata BM, Hutchinson GB, Wu K, Henry C, Bahl K, Garcia-Dominguez D, Ma L, Renzi I, Kong WP, Schmidt SD, Wang L, Zhang Y, Phung E, Chang LA, Loomis RJ, Altaras NE, Narayanan E, Metkar M, Presnyak V, Liu C, Louder MK, Shi W, Leung K, Yang ES, West A, Gully KL, Stevens LJ, Wang N, Wrapp D, Doria-Rose NA, Stewart-Jones G, Bennett H, Alvarado GS, Nason MC, Ruckwardt TJ, McLellan JS, Denison MR, Chappell JD, Moore IN, Morabito KM, Mascola JR, Baric RS, Carfi A, Graham BS. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 2020, 586: 567-571. PMID: 32756549, DOI: 10.1038/s41586-020-2622-0.
  • Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques.Mercado NB, Zahn R, Wegmann F, Loos C, Chandrashekar A, Yu J, Liu J, Peter L, McMahan K, Tostanoski LH, He X, Martinez DR, Rutten L, Bos R, van Manen D, Vellinga J, Custers J, Langedijk JP, Kwaks T, Bakkers MJG, Zuijdgeest D, Rosendahl Huber SK, Atyeo C, Fischinger S, Burke JS, Feldman J, Hauser BM, Caradonna TM, Bondzie EA, Dagotto G, Gebre MS, Hoffman E, Jacob-Dolan C, Kirilova M, Li Z, Lin Z, Mahrokhian SH, Maxfield LF, Nampanya F, Nityanandam R, Nkolola JP, Patel S, Ventura JD, Verrington K, Wan H, Pessaint L, Van Ry A, Blade K, Strasbaugh A, Cabus M, Brown R, Cook A, Zouantchangadou S, Teow E, Andersen H, Lewis MG, Cai Y, Chen B, Schmidt AG, Reeves RK, Baric RS, Lauffenburger DA, Alter G, Stoffels P, Mammen M, Van Hoof J, Schuitemaker H, Barouch DH. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature 2020, 586: 583-588. PMID: 32731257, DOI: 10.1038/s41586-020-2607-z.
  • Potently neutralizing and protective human antibodies against SARS-CoV-2.Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schäfer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr. Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature 2020, 584: 443-449. PMID: 32668443, DOI: 10.1038/s41586-020-2548-6.
  • Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants.Martinez DR, Tu JJ, Kumar A, Mangold JF, Mangan RJ, Goswami R, Giorgi EE, Chen J, Mengual M, Douglas AO, Heimsath H, Saunders KO, Nicely NI, Eudailey J, Hernandez G, Morgan-Asiedu PK, Wiehe K, Haynes BF, Moody MA, LaBranche C, Montefiori DC, Gao F, Permar SR. Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants. MBio 2020, 11 PMID: 32156815, DOI: 10.1128/mBio.00176-20.
  • The Impact of IgG transplacental transfer on early life immunity.Fouda GG, Martinez DR, Swamy GK, Permar SR. The Impact of IgG transplacental transfer on early life immunity. Immunohorizons 2018, 2: 14-25. PMID: 29457151, DOI: 10.4049/immunohorizons.1700057.
  • Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk.Martinez DR, Vandergrift N, Douglas AO, McGuire E, Bainbridge J, Nicely NI, Montefiori DC, Tomaras GD, Fouda GG, Permar SR. Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk. J Virol 2017, 91 PMID: 28202762, DOI: 10.1128/JVI.02422-16.
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