Neutralizing antibodies from prior exposure to dengue virus negatively correlate with viremia on re-infection

Anbalagan Anantharaj; Tanvi Agrawal; Pooja Kumari Shashi; Alok Tripathi; PARVEEN KUMAR; Imran Khan; Madhu Pareek; Balwant Singh; Chitra Pattabiraman; Saurabh Kumar; Rajesh Pandey; Anmol Chandele; Rakesh Lodha; Stephen S. Whitehead; Guruprasad R. Medigeshi

doi:10.1038/s43856-023-00378-7

journal article Open Access Oct 19, 2023

Neutralizing antibodies from prior exposure to dengue virus negatively correlate with viremia on re-infection

Anbalagan Anantharaj Tanvi Agrawal

Pooja Kumari Shashi Alok Tripathi PARVEEN KUMAR

Imran Khan

Madhu Pareek Balwant Singh

Chitra Pattabiraman Saurabh Kumar

Rajesh Pandey Anmol Chandele Rakesh Lodha Stephen S. Whitehead

Guruprasad R. Medigeshi

Communications Medicine Vol. 3 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s43856-023-00378-7

Abstract

Abstract

Background
India is hyperendemic to dengue and over 50% of adults are seropositive. There is limited information on the association between neutralizing antibody profiles from prior exposure and viral RNA levels during subsequent infection.

Methods
Samples collected from patients with febrile illness was used to assess seropositivity by indirect ELISA. Dengue virus (DENV) RNA copy numbers were estimated by quantitative RT-PCR and serotype of the infecting DENV was determined by nested PCR. Focus reduction neutralizing antibody titer (FRNT) assay was established using Indian isolates to measure the levels of neutralizing antibodies and also to assess the cross-reactivity to related flaviviruses namely Zika virus (ZIKV), Japanese encephalitis virus (JEV) and West Nile virus (WNV).

Results

In this cross-sectional study, we show that dengue seropositivity increased from 52% in the 0–15 years group to 89% in >45 years group. Antibody levels negatively correlate with dengue RNAemia on the day of sample collection and higher RNAemia is observed in primary dengue as compared to secondary dengue. The geometric mean FRNT
50
titers for DENV-2 is significantly higher as compared to the other three DENV serotypes. We observe cross-reactivity with ZIKV and significantly lower or no neutralizing antibodies against JEV and WNV. The FRNT
50
values for international isolates of DENV-1, DENV-3 and DENV-4 is significantly lower as compared to Indian isolates.

Conclusions
Majority of the adult population in India have neutralizing antibodies to all the four DENV serotypes which correlates with reduced RNAemia during subsequent infection suggesting that antibodies can be considered as a good correlate of protection.

Topics

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References

57

[1]

Lustig, Y., Wolf, D., Halutz, O. & Schwartz, E. An outbreak of dengue virus (DENV) type 2 Cosmopolitan genotype in Israeli travellers returning from the Seychelles, April 2017. Euro. Surveill. 22, 30563 (2017). 10.2807/1560-7917.es.2017.22.26.30563

[2]

Dengue

Cameron P. Simmons, Jeremy J. Farrar, Nguyen van Vinh Chau et al.

New England Journal of Medicine 10.1056/nejmra1110265

[3]

The global distribution and burden of dengue

Samir Bhatt, Peter W. Gething, Oliver J. Brady et al.

Nature 2013 10.1038/nature12060

[4]

Organization W. H., Research SPf, Diseases TiT, Diseases WHODoCoNT, Epidemic WHO, Alert P. Dengue: guidelines for diagnosis, treatment, prevention and control: World Health Organization; 2009.

[5]

Stanaway, J. D. et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet 388, 1081–1088 (2016). 10.1016/s0140-6736(16)30579-7

[6]

Kumar, P. S. S., Arjun, M. & Gupta, S. K. Nongkynrih BJIJoMS. Malaria, dengue and chikungunya in India–An update 9, 25–29 (2018).

[7]

Gupta, E. & Ballani, N. Current perspectives on the spread of dengue in India. Infect. Drug Resist. 7, 337–342 (2014). 10.2147/idr.s55376

[8]

Anoop, M. et al. Complete genome sequencing and evolutionary analysis of dengue virus serotype 1 isolates from an outbreak in Kerala, South India. Virus Genes 45, 1–13 (2012). 10.1007/s11262-012-0756-3

[9]

Holmes, E. C. & Twiddy, S. S. The origin, emergence and evolutionary genetics of dengue virus. Infect. Genet. Evol. 3, 19–28 (2003). 10.1016/s1567-1348(03)00004-2

[10]

Jain, R., Sontisirikit, S., Iamsirithaworn, S. & Prendinger, H. Prediction of dengue outbreaks based on disease surveillance, meteorological and socio-economic data. BMC Infect. Dis. 19, 272 (2019). 10.1186/s12879-019-3874-x

[11]

Rodríguez-Aguilar, E. D. et al. Genetic diversity and spatiotemporal dynamics of DENV-1 and DENV-2 infections during the 2012-2013 outbreak in Mexico. Virology 573, 141–50 (2022). 10.1016/j.virol.2022.06.011

[12]

Inizan, C. et al. Viral evolution sustains a dengue outbreak of enhanced severity. Emerg. Microbes Infect. 10, 536–44 (2021). 10.1080/22221751.2021.1899057

[13]

Wen, S. et al. Complete Genome Characterization of the 2017 Dengue Outbreak in Xishuangbanna, a Border City of China, Burma and Laos. Front. Cell Infect. Microbiol. 8, 148 (2018). 10.3389/fcimb.2018.00148

[14]

Descloux, E., Cao-Lormeau, V. M., Roche, C. & De Lamballerie, X. Dengue 1 diversity and microevolution, French Polynesia 2001-2006: connection with epidemiology and clinics. PLoS Negl. Trop. Dis. 3, e493 (2009). 10.1371/journal.pntd.0000493

[15]

Hadinegoro, S. R. et al. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. N. Engl. J. Med. 373, 1195–1206 (2015). 10.1056/nejmoa1506223

[16]

Organization, W. H. Dengue vaccine: WHO position paper - September 2018. Weekly Epidemiol. Record 93, 457–476 (2018).

[17]

Murhekar, M. V. et al. Burden of dengue infection in India, 2017: a cross-sectional population based serosurvey. Lancet Glob. Health 7, e1065–e73 (2019). 10.1016/s2214-109x(19)30250-5

[18]

Mishra, A. C. et al. Stratified sero-prevalence revealed overall high disease burden of dengue but suboptimal immunity in younger age groups in Pune, India. PLoS Negl. Trop. Dis. 12, e0006657 (2018). 10.1371/journal.pntd.0006657

[19]

Garg, S. et al. Dengue serotype-specific seroprevalence among 5- to 10-year-old children in India: a community-based cross-sectional study. Int. J. Infect. Dis. 54, 25–30 (2017). 10.1016/j.ijid.2016.10.030

[20]

Kar, M. et al. Isolation and molecular characterization of dengue virus clinical isolates from pediatric patients in New Delhi. Int. J. Infect. Dis. 84S, S25–S33 (2019). 10.1016/j.ijid.2018.12.003

[21]

Blaney, J. E. Jr. et al. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am. J. Trop. Med. Hyg. 71, 811–821 (2004). 10.4269/ajtmh.2004.71.811

[22]

Puri, B., Polo, S., Hayes, C. G. & Falgout, B. Construction of a full length infectious clone for dengue-1 virus Western Pacific,74 strain. Virus Genes 20, 57–63 (2000). 10.1023/a:1008160123754

[23]

Whitehead, S. S. et al. A live, attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide deletion in the 3’ untranslated region is highly attenuated and immunogenic in monkeys. J. Virol. 77, 1653–1657 (2003). 10.1128/jvi.77.2.1653-1657.2003

[24]

Haridas, V. et al. Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. PLoS Negl. Trop. Dis. 7, e2005 (2013). 10.1371/journal.pntd.0002005

[25]

Klungthong, C. et al. Monitoring and improving the sensitivity of dengue nested RT-PCR used in longitudinal surveillance in Thailand. J. Clin. Virol. 63, 25–31 (2015). 10.1016/j.jcv.2014.12.009

[26]

Bewley, K. R. et al. Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays. Nat. Protoc. 16, 3114–40. (2021). 10.1038/s41596-021-00536-y

[27]

Singla, M. et al. Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India–Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity. PLoS Negl. Trop. Dis. 10, e0004497 (2016). 10.1371/journal.pntd.0004497

[28]

Raafat, N., Blacksell, S. D. & Maude, R. J. A review of dengue diagnostics and implications for surveillance and control. Trans. R Soc. Trop. Med. Hyg. 113, 653–60. (2019). 10.1093/trstmh/trz068

[29]

Tricou, V., Minh, N. N., Farrar, J., Tran, H. T. & Simmons, C. P. Kinetics of Viremia and NS1 Antigenemia Are Shaped by Immune Status and Virus Serotype in Adults with Dengue. PLOS Negl. Trop. Dis. 5, e1309 (2011). 10.1371/journal.pntd.0001309

[30]

Islam, A. et al. Circulation of dengue virus serotypes in hyperendemic region of New Delhi, India during 2011-2017. J. Infect Public Health 13, 1912–1919 (2020). 10.1016/j.jiph.2020.10.009

[31]

Kar, M. et al. Dengue Virus Entry and Replication Does Not Lead to Productive Infection in Platelets. Open Forum Infect Dis. 4, ofx051 (2017). 10.1093/ofid/ofx051

[32]

Parveen, N. et al. Circulation of single serotype of Dengue Virus (DENV-3) in New Delhi, India during 2016: A change in the epidemiological trend. J. Infect Public Health 12, 49–56 (2019). 10.1016/j.jiph.2018.08.008

[33]

Chan, K. R. et al. Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection. Proc. Natl. Acad. Sci. USA. 108, 12479–12484 (2011). 10.1073/pnas.1106568108

[34]

Wahala, W. M. & Silva, A. M. The human antibody response to dengue virus infection. Viruses 3, 2374–2395 (2011). 10.3390/v3122374

[35]

de Alwis, R. et al. In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection. PLoS Negl. Trop. Dis. 5, e1188 (2011). 10.1371/journal.pntd.0001188

[36]

Katzelnick, L. C. et al. Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term. Sci. Transl. Med. 13, eabg9478 (2021). 10.1126/scitranslmed.abg9478

[37]

Chowdhury, P. & Khan, S. A. Global emergence of West Nile virus: Threat & preparedness in special perspective to India. Indian J. Med. Res. 154, 36–50 (2021). 10.4103/ijmr.ijmr_642_19

[38]

Walsh, M. G. et al. High-risk landscapes of Japanese encephalitis virus outbreaks in India converge on wetlands, rain-fed agriculture, wild Ardeidae, and domestic pigs and chickens. Int. J. Epidemiol. 51, 1408–18 (2022). 10.1093/ije/dyac050

[39]

Rathore, A. P. S. et al. Cross-Reactive Immunity Among Flaviviruses. Front. Immunol. 11, 334 (2020). 10.3389/fimmu.2020.00334

[40]

Waman, V. P., Kolekar, P., Ramtirthkar, M. R., Kale, M. M. & Kulkarni-Kale, U. Analysis of genotype diversity and evolution of Dengue virus serotype 2 using complete genomes. Peer J. 4, e2326 (2016). 10.7717/peerj.2326

[41]

Waman, V. P., Kasibhatla, S. M., Kale, M. M. & Kulkarni-Kale, U. Population genomics of dengue virus serotype 4: insights into genetic structure and evolution. Arch. Virol. 161, 2133–2148 (2016). 10.1007/s00705-016-2886-8

[42]

Jagtap, S., Pattabiraman, C., Sankaradoss, A., Krishna, S. & Roy, R. Evolutionary dynamics of dengue virus in India. PLoS Pathog. 19, e1010862 (2023). 10.1371/journal.ppat.1010862

[43]

Sankaradoss, A. et al. Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences. Mol. Ther. 30, 2058–77 (2022). 10.1016/j.ymthe.2022.01.013

[44]

Torres-Flores, J. M., Reyes-Sandoval, A. & Salazar, M. I. Dengue Vaccines: An Update. Bio. Drugs 36, 325–36. (2022).

[45]

Wilder-Smith, A. Dengue vaccine development by the year 2020: challenges and prospects. Curr. Opin. Virol. 43, 71–78 (2020). 10.1016/j.coviro.2020.09.004

[46]

Buddhari, D. et al. Dengue virus neutralizing antibody levels associated with protection from infection in thai cluster studies. PLoS Negl. Trop. Dis. 8, e3230 (2014). 10.1371/journal.pntd.0003230

[47]

Katzelnick, L. C., Montoya, M., Gresh, L., Balmaseda, A. & Harris, E. Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort. Proc. Natl. Acad. Sci. USA. 113, 728–733 (2016). 10.1073/pnas.1522136113

[48]

Lambrechts, L. et al. Dengue-1 virus clade replacement in Thailand associated with enhanced mosquito transmission. J. Virol. 86, 1853–1861 (2012). 10.1128/jvi.06458-11

[49]

Adams, B. et al. Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok. Proc. Natl. Acad. Sci. USA. 103, 14234–14239 (2006). 10.1073/pnas.0602768103

[50]

OhAinle, M. et al. Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity. Sci. Transl. Med. 3, 114ra28 (2011). 10.1126/scitranslmed.3003084

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Published: Oct 19, 2023
Vol/Issue: 3(1)
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Authors

Centro de Investigación en Ciencias del Mar y Limnología (CIMAR)/Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas, 177, 4050-123 Porto, Portugal.; Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.

INHS Asvini, Mumbai, Maharashtra, India

Guruprasad R. Medigeshi

Cite This Article

Anbalagan Anantharaj, Tanvi Agrawal, Pooja Kumari Shashi, et al. (2023). Neutralizing antibodies from prior exposure to dengue virus negatively correlate with viremia on re-infection. Communications Medicine, 3(1). https://doi.org/10.1038/s43856-023-00378-7

Neutralizing antibodies from prior exposure to dengue virus negatively correlate with viremia on re-infection

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