1

Development of innovative vaccines for diseases of pigs (African Swine Fever, PRRS) and Cattle (Lumpy Skin diseases),(In communication).

The following projects are completed during my PhD period in the United States of America.

1

Development and evaluation of efficacy of novel Porcine Reproductive and respiratory Syndrome (PRRS) virus vaccine candidates in Pigs.

a) Developed and evaluated the protective efficacy of novel vaccine formulations like PRRS Virus like particles (PRRS-VLP), mutant live PRRSV vaccines in pigs.

b) Tested the vaccination strategies for live PRRS vaccines and application of genetically modified non-toxic enterotoxin and E. coli as vaccine adjuvants for killed vaccines formulations against PRRSV in a collaborative research project.

c) Development of Vesicular Stomatitis Virus (VSV) vector based recombinant PRRSV vaccines by reverse genetics.

d) Major contributor in development and efficacy testing ofnano-particle based vaccines against Swine influenza virus in pigs, salmonella vaccines in poultry & Influenza virus infection study on infant microflora in humanized piglet model.

2

Development the novel ways to design an HIV vaccine and understand the HIV pathogenesis in human, non-human primates (NHP) and mouse model systems using flow cytometry-based assays.

a) Performed a study on age related neurodegenerative disorder after Anti Retro Viral Therapy (ART) in HIV+ patients using NHP models to determine the role Th1, Th17, Tfh CD4 T-cells during neuroinflammation and neurodegeneration.

b) Dissected the immunobiology of α4β7+ and α4β7- CD4 T cell subsets and their susceptibility to HIV acquisition. Explored vaccine effects on target α4β7+ CD4 T cells in the female genital tract (FGT) mucosa.

c) Evaluated the central memory T cells/T cell repertoires of the central nervous system (CNS) using 10X genomics, Single cell RNA Seq in rhesus macaques and SMARTer transgenic mice models to study the neurodegeneration and neuroinflammation.

3

Dissecting the immunology and pathogenesis of SARS CoV2 in aged, young, and nursing macaques.

a) Used the convalescent plasma as a treatment in pre and post SARS-CoV-2 infected adult and young rhesus macaques during the early onset of COVID and studied of pathogenesis of SARS-CoV-2 Delta variant in aged, nursing mothers and young rhesus macaques.

b) Tested the efficacy of anti-SARS-CoV-2 monoclonal antibodies in pre and post exposure rhesus macaques.

c) Evaluated the efficacy of SARS-CoV-2 mRNA vaccines after challenge with SARS-CoV2 variants (Delta variant) in rhesus macaques.

1

Yashavanth Shaan Lakshmanappa, Sonny R Elizaldi, Jamin W Roh, Brian A Schmidt, Timothy D Carroll, Kourtney D Weaver, Justin C Smith, Anil Verma, Jesse D Deere, Joseph Dutra, Mars Stone, Sergej Franz, Rebecca Lee Sammak, Katherine J Olstad, J Rachel Reader, Zhong-Min Ma, Nancy K Nguyen, Jennifer Watanabe, Jodie Usachenko, Ramya Immareddy, JoAnn L Yee, Daniela Weiskopf, Alessandro Sette, Dennis Hartigan-O’Connor, Stephen J McSorley, John H Morrison, Nam K Tran, Graham Simmons, Michael P Busch, Pamela A Kozlowski, Koen KA Van Rompay, Christopher J Miller, Smita S Iyer, SARS-CoV-2 infection induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques. (Nature Communications, January 2021 Vol 12, Issue 1, pp 1-14 IF:14.919)

2

Yashavanth S Lakshmanappa, Jamin W Roh, Niharika N Rane, Ashok R Dinasarapu, Daphne D Tran, Vijayakumar Velu, Anandi N Sheth, Igho Ofotokun, Rama R Amara, Colleen F Kelley, Elaine Waetjen, Smita S Iyer Circulating integrin α4β7+ CD4 T cells are enriched for proliferative transcription programs in HIV infection (FEBS letters, July 2021,Vol 595, Issue 17, pp 2257-2270 IF: 4.0 DOI: 10.1002/1873-3468.14163)

3

Anil Verma, Chase E Hawes, Yashavanth Shaan Lakshmanappa, Jamin W Roh, Brian A Schmidt, Joseph Dutra, William Louie, Hongwei Liu, Zhong-Min Ma, Jennifer K Watanabe, Jodie L Usachenko, Ramya Immareddy, Rebecca L Sammak, Rachel Pollard, J Rachel Reader, Katherine J Olstad, Lark L Coffey, Pamela A Kozlowski, Dennis J Hartigan-O’Connor, Michel Nussenzweig, Koen KA Van Rompay, John H Morrison, Smita S Iyer , Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2 associated immune activation (Cell reports, November 2021, Vol 37, Issue 5 PP109942, IF: 9.4)

4

Emma C. Milligan, Katherine Olstad, Caitlin A. Williams, Michael Mallory, Patricio Cano, Kaitlyn A. Cross, Jennifer E. Munt, Carolina Garrido, Lisa Lindesmith, Jennifer Watanabe, Jodie L. Usachenko, Lincoln Hopkins, Ramya Immareddy, Yashavanth Shaan Lakshmanappa, Sonny R. Elizaldi, Jamin W. Roh, Rebecca L Sammak, JoAnn L. Yee, Savannah Herbek, Trevor Scobey, Dieter Miehlke, Genevieve Fouda, Guido Ferrari, Hongmei Gao, Xiaoying Shen, Pamela A. Kozlowski, David Montefiori, Michael Hudgens, Darin K. Edwards, Andrea Carfi, Kizzmekia S. Corbett, Barney S. Graham, Christopher B. Fox, Mark Tomai, Smita S. Iyer, Ralph Baric, Rachel Reader, Dirk P. Dittmer, Koen K.A. Van Rompay, Sallie Permar, and Kristina De Paris: Protection of SARS-CoV-2 immunized infant rhesus macaques against lung inflammation after heterologous virus challenge one year later ( Science Translational Medicine, December 2022, IF: 17.9)

5

Chase E. Hawes, Sonny R. Elizaldi, Danielle Beckman, Giovanne B. Diniz, Yashavanth Shaan Lakshmanappa, Sean Ott, Blythe P. Durbin-Johnson, Ashok R. Dinasarapu, Andrea Gompers, John H. Morrison, Smita S. Iyer : Neuroinflammatory transcriptional programs induced in rhesus pre frontal cortex white matter during acute SHIV infection ( Journal of Neuroinflammation October 2022, IF: 7.6)

6

Stephanie N. Langel, Carolina Garrido, Caroline Phan, Tatianna Travies, Todd DeMarco, Zhong Min Ma, Rachel Reader, Katherine J. Olstad, Rebecca L. Sammak, Yashavanth Shaan Lakshmanappa, Jamin W. Roh, Jennifer Watanabe, Jodie Usachenko, Ramya Immareddy, Rachel Pollard, Smita S. Iyer, Sallie Permar, Lisa A. Miller, Koen K.A. Van Rompay and Maria Blasi: Distinct upper airway epithelium interferon-stimulated and profibrotic gene expression between adult and infant rhesus macaques infected with SARS-CoV-2 (Journal of ImmunoHorizon, December 2022, IF: 3.0)

7

Jesse D. Deere, Timothy D. Carroll, Joseph Dutra, Linda Fritts, Rebecca Lee Sammak, JoAnn L. Yee, Katherine J. Olstad, J. Rachel Reader, Amy Kistler, Jack Kamm, Clara Di Germanio, Yashavanth Shaan Lakshmanappa, Sonny R. Elizaldi, JaminW.Roh, GrahamSimmons, JenniferWatanabe, RachelE.Pollard, JodieUsachenko, Ramya Immareddy, BrianA.Schmidt, Shelby L. O’Connor, Joseph DeRisi, Michael P. Busch, Smita S. Iyer, Koen K. A. Van Rompay, Dennis J. Hartigan-O’Connor, Christopher J. Millerb, SARS-CoV-2 infection of rhesus macaques treated early with human COVID-19 convalescent plasma. (Microbial Spectrum, November, 2021, Vol 9 Issue 3, IF: 7.17)

8

Koen K. A. Van Rompay, Katherine Olstad, Rebecca L. SammakID, Joseph Dutra, Jennifer K. Watanabe, Jodie L. Usachenko, Ramya Immareddy, Anil Verma, Yashavanth Shaan Lakshmanappa, Brian A. Schmidt, Jamin W. Roh, Sonny R. Elizaldi, A. Mark Allen, Frauke MueckschI, Julio C. C. LorenziI, Sarah Lockwood, Rachel E. Pollard, JoAnn L. Yee, Peter B. Nham, Amir Ardeshir, Jesse D. Deere, Jean Patterson, Que Dang, Theodora Hatziioannou, Paul D. Bieniasz, Smita S. Iyer, Dennis J. HartiganO’Connor, Michel C. Nussenzweig, J. Rachel Reader, Early treatment with a combination of two potent neutralizing antibodies improves clinical outcomes and reduces virus replication and lung inflammation in SARS-CoV-2 infected macaques ( PLoS Pathogen, July, 2021 IF: 6.8)

9

Koen KA Van Rompay, Katherine J Olstad, Rebecca L Sammak, Joseph Dutra, Jennifer K Watanabe, Jodie L Usachenko, Ramya Immareddy, Jamin W Roh, Anil Verma, Yashavanth Shaan Lakshmanappa, Brian A Schmidt, Clara Di Germanio, Nabeela Rizvi, Mars Stone, Graham Simmons, Larry J Dumont, A Mark Allen, Sarah Lockwood, Rachel E Pollard, Rafael Ramiro De Assis, JoAnn L Yee, Peter B Nham, Amir Ardeshir, Jesse D Deere, Jean Patterson, Aarti Jain, Philip L Felgner, Smita S Iyer, Dennis J Hartigan-Oâ, , Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity reduces lung inflammation. (PLoS Pathogen, 2022, IF:6.8)

10

Sankar Renu, Loic Deblais, Veerupaxagouda Patil, Jennifer Schrock, Dipak Kathayat, Vishal Srivastava, Ninoshkaly Feliciano-Ruiza, Yi Han, Anikethana Ramesh, Yashavanth S Lakshmanappa, Shristi Ghimire, Santosh Dhakal, Gireesh Rajashekara and Gourapura J Renukaradhya Gut Microbiota of obese children influences inflammatory mucosal immune pathways in the respiratory tract to influenza virus infection: optimization of an ideal duration of microbial colonization in a gnotobiotic pig model : Microbiology Spectrum 10(3), May 2022 IF :7.17

11

Gokben Ozbey, Alfizah Hanafiah,Yashavantth Shaan Lakshmanappa, Santosh Dhakal, Gourapura J Renukaradhya,:Insights to the epidemiology, diagnosis and treatments of SARS-CoV2; International Journal of Molecular and Clinical Microbiology (IJMCM) 12(2) August 2022: 1684 1691)

12

Gokben Ozbey, Alfizah Hanafiah, Yashavantth Shaan Lakshmanappa, Santosh Dhakal, Gourapura J Renukaradhya,: The Genome characteristics of SARS CoV2 and emergence of SARS CoV2: International Journal of Molecular and Clinical Microbiology (IJMCM) January 2023)

13

Gokben Ozbey, Elif Seren Tanriverdi, Asiye Basusta, Yashvanth Shaan Lakshmanappa, Baris Otlu, František Zigo, Investigation for the presence of bacteria and antimicrobial resistance genes in sea snails (Rapana venosa) Annals of Agricultural and Environmental Medicine, June 2023

14

Sankar Renu, Yi Han, Santosh Dhakal, Yashavanth S Lakshmanappa, Shristi Ghimire, Ninoshkaly Feliciano-Ruiza, Sujata Senapati, Balaji Narasimhan, Ramesh Selvaraj and Gourapura J Renukaradhya Chitosan-adjuvanted Salmonella subunit nanoparticle vaccine for poultry delivered through drinking water and feed. Carbohydrate Polymers 243:116434, May 2020 IF: 9.38)

15

Anil Verma, Brian A. Schmidt, Sonny R. Elizaldi, Nancy K. Nguyen, Korey A. Walter, Zoltan Beck, Hung V. Trinh, Ashok R. Dinasarapu, Yashavanth Shaan Lakshmanappa, Niharika N. Rane, Gary R. Matyas, Mangala Rao, Xiaoying Shen, Georgia D. Tomaras Celia C. LaBranche, Keith A. Reimann, David H. Foehl, Johannes S. Gach, Donald N. Forthal, Pamela A. Kozlowski, Rama R. Amara, Smita S. Iyer,: Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques: (Journal of Virology, February 2020 Issue 6, Vol 94, IF: )

16

Santosh Dhakal; Lingling Wang; Linto Antony; Jennifer Rank; Pauline Bernardo; Shristi Ghimire; Kathy Bondra; Christina Siems; Yashavanth Shaan Lakshmanappa; Renu Sankar; Bradley Hogshead; Steven Krakowka; Mike Kauffman; Joy Scaria; Jeffrey Lejeune; Zhongtang Yu; and Gourapura J. Renukaradhya, Amish(Rural) versus non-Amish (urban) infant fecal microbiotas are highly diverse and transplantation lead to differences in mucosal immune maturation in the humanized germfree piglet model; (Front. Immunol 16 July 2019; I.F 5.085)

17

S Dhakal, S Ghimire, S Renu, K.A.Ross, Y.S.Lakshmanappa, B.T.Hogshead, P.Bernardo, C.W.Lee, M.J.Wannermuehhler, B Narasimhan, G.J.Renukaradhya Evaluation of CpG-ODN-adjuvanted polyanhydride-based intranasal influenza nanovaccine in pigs (Veterinary Microbiology, Vol 237, October 2019; IF: 3.24)

18

Basavaraj Binjawadagi, Yashavanth Shaan Lakshmanappa, Zhu Longchao,Santosh Dhakal,Jagadish Hiremath, Kang Ouyang, Duan-Liang Shyu, Jesus Arcos, Shang Pengcheng, Aaron Gilbertie,Federico Zuckermann, Jordi B. Torrelles, Daral Jackwood,Ying Fang, Gourapura J. Renukaradhya, Development of a porcine reproductive and respiratory syndrome virus-like particle-based vaccine and evaluation of its immunogenicity in pigs. Archives of Virology, June 2016, Volume 161, Issue 6, pp 1579–1589. I.F : 2.11

19

Rui Guo, Pengcheng Shang, Celena A Carrillo, Zhi Sun, Yashavanth S Lakshmanappa, Xingyu Yan, Gourapura J Renukaradhya, Jodi McGill, Crystal J Jaing, Megan C Niederwerder, Raymond R Rowland, Double-stranded viral RNA persists in vitro and in vivo during prolonged infection of porcine reproductive and respiratory syndrome virus.: Virology , 2018 I.F: 3.353.

20

Santosh Dhakal, Sankar Renu, Shristi Ghimire, Yashavanth Shaan Lakshmanappa, Bradley Hogshead, Ninoshkaly Feliciano Ruiz,Steven Krakowka,Chang Won Lee and Renukaradhya J Gourapura* Mucosal immunity and protective efficacy of inactivated influenza virus vaccine is improved by using the intranasal chitosan delivery system in pigs. Frontiers of Immunology, 2018: I.F: 6.424

21

Sankar Renu, Santosh Dhakal, Jonathan Goodman, Yashavanth Shaan Lakshmanappa, Eunsoo Kim, Michael Wannemuehler, Balaji Narasimhan, Prosper Boyaka and Renukaradhya J Gourapura. Differential expression of B cell activation factor regulates breadth of antibody responses to nanoparticle-based nasal vaccines. Cellular Immunology, 2018: I.F: 2.14

22

Santosh Dhakal; Fangjia Lu; Shristi Ghimire; Sankar Renu; Yashavanth Shaan Lakshmanappa; Bradley Hogshead; Darryl Ragland; Harm Hogenesch, and Renukaradhya Gourapura. Corn derived alpha-D-glucan nanoparticles as adjuvant for intramuscular and intranasal immunization in pigs. Nanomedicine. 2019 Feb;16: 226-235. I.F: 6.5.

23

Santosh Dhakal; Xingguo Cheng; Renu Sankar; Yashavanth Shaan Lakshmanappa; Bradley Hogshead; Kathy Bondra; Nino Feliciano-Ruiz ; Steve Krakowka; Chang Won Lee. Liposome nanoparticle-based influenza conserved peptides vaccine and monosodium urate crystal adjuvant elicits protective immune response in pigs. Int J Nanomedicine. 2018 Oct 24;13:6699-6715 I.F: 4.383.

24

Santosh Dhakal, Jagadish Hiremath, Kathryn Bondra, Yashavanth S Lakshmanappa, DuanLiang Shyu, Kang Ouyang, Kyung-il Kang, Basavaraj Binjawadagi, Jonathan Goodman, Kairat Tabynov, Steven Krakowka, Balaji Narasimhan, Chang Won Lee, Gourapura J. Renukaradhya. Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell mediated immune response in pigs. Journal Control Release, Volume 247, 2017, Pages 194–205. I.F: 7.705

25

Santosh Dhakal, Jonathan Goodman, Kathryn Bondra, Yashavanth S Lakshmanappa, Jagadish Hiremath, Duan-Liang Shyu, Kang Ouyang, Kyung-il Kang, Steven Krakowka, Michael J. Wannemuehler, Chang Won Lee, Balaji Narasimhan, Gourapura J. Renukaradhya. Polyanhydride nanovaccine against swine influenza virus in pigs. Vaccine, January 2017. I.F: 3.235

26

Sankar Renu, Ashley Markazi, Santosh Dhakal, Yashavanth shaan lakshmanappa, Revathi Shanmugasundaram, Ramesh Selvaraj Gourapura J Renukaradhya. Oral deliverable Mucoadhesive chitosan-Salmonella subunit nanovaccine for layer chickens. International Journal of Nanomedicine February 2020; Vol 15, pp 761-777, IF : 5.93)

27

Renu Sankar, Markazi Ashley, Santosh Dhakal, Yashavanth Shaan Lakshmanappa, Suren Gourapura; Revathi Shanmugasundaram, Sujata Senapati, Balaji Narasimhan, Gourapura J Renukaradhya. Surface engineered polyanhydride based oral Salmonella subunit nanovaccine for poultry Renukaradhya Gourapura International Journal of Nanomedicine-2018, Nov 30:13:8195 8215. I.F : 4.383

28

Kang Ouyang, Duan-Liang Shyu, Santosh Dhakal, Jagadish Hiremath, Basavaraj Binjawadagi, Yashavanth S Lakshmanapp Rui Guo, Russell Ransburgh, Kathryn M Bondra, Phillip Gauger, Jianqiang Zhang, Terry Spencht, Aaron Gilbertie, William Minton, Ying Fang and Renukaradhya J Gourapura . Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions. Veterinary Research, 2015, 46:140. I.F : 2.798

29

Yashavanth Shaan Lakshmanappa, Majee S.B. Sherikar A.A, GENE BANK Submission of Partial Sequence of Gallid Herpes Virus2 isolate MDV-BVCMICRO1 from India BamHI repeat region, with accession#EF408266.

30

Amitha R. Gomes, RaveendraHegde, S.M.Byregowda, Suryanarayana T, Ananda H, Yashavant S.L., s P. Giridhar and C. Renukaprasad. PCR based confirmation of sheeppox vaccine virus. Veterinary World. 3 (2) 2010.

31

Amitha R. Gomes, RaveendraHegde, S.M.Byregowda, VijayashreeVaradarajan, Yashawant S. L, Giridhar, P and C. Renukaprasad. 2010 (Sept-Oct) Evaluation of humoral immune response to sheeppox vaccine. Tamilnadu Journal of Veterinary and Animal Sciences. 6(5) 236-238.

32

M.S.Dinesh, Chandana P.G, Geetha K.S, Byregowda S.M, Yashwanth S. L and V. Krishnamurthy, Anticancerous potential of peptides of coelomic fluid of Eudriluseugeniae. Journal of Biochemical Technology Vol 8 (1).

2

< Indian J. Comp. Microbiol. Immunol. Infect. Dis., 42(2): 110-122.