TY - JOUR

T1 - Multilevel comparison of Indian Naja venoms and their cross-reactivity with Indian polyvalent antivenoms

AU - Deka, Archana

AU - Bhatia, Siddarth

AU - Santra, Vishal

AU - Bharti, Omesh

AU - Lalremsanga, Hmar

AU - Martin, Gerard

AU - Wüster, Wolfgang

AU - Owens, John Benjamin

AU - Graham, Stuart

AU - Doley, Robin

AU - Malhotra, Anita

PY - 2023/4/1

Y1 - 2023/4/1

N2 - Snake envenoming is caused by many biological species, rather than a single infectious agent, each with a multiplicity of toxins in their venom. Hence, developing effective treatments is challenging, especially in biodiverse and biogeographically complex countries such as India. The present study represents the first genus-wide proteomics analysis of venom composition across Naja species (N. naja, N. oxiana, and N. kaouthia) found in mainland India. Venom proteomes were consistent between individuals from the same localities in terms of the toxin families present, but not in the relative abundance of those in the venom. There appears to be more compositional variation among N. naja from different locations than among N. kaouthia. Immunoblotting and in vitro neutralization assays indicated cross-reactivity with Indian polyvalent antivenom, in which antibodies raised against N. naja are present. However, we observed ineffective neutralization of PLA2 activities of N. naja venoms from locations distant from the source of immunizing venoms. Antivenom immunoprofiling by antivenomics revealed differential antigenicity of venoms from N. kaouthia and N. oxiana, and poor reactivity towards 3FTxs and PLA2s. Moreover, there was considerable variation between antivenoms from different manufacturers. These data indicate that improvements to antivenom manufacturing in India are highly desirable.

AB - Snake envenoming is caused by many biological species, rather than a single infectious agent, each with a multiplicity of toxins in their venom. Hence, developing effective treatments is challenging, especially in biodiverse and biogeographically complex countries such as India. The present study represents the first genus-wide proteomics analysis of venom composition across Naja species (N. naja, N. oxiana, and N. kaouthia) found in mainland India. Venom proteomes were consistent between individuals from the same localities in terms of the toxin families present, but not in the relative abundance of those in the venom. There appears to be more compositional variation among N. naja from different locations than among N. kaouthia. Immunoblotting and in vitro neutralization assays indicated cross-reactivity with Indian polyvalent antivenom, in which antibodies raised against N. naja are present. However, we observed ineffective neutralization of PLA2 activities of N. naja venoms from locations distant from the source of immunizing venoms. Antivenom immunoprofiling by antivenomics revealed differential antigenicity of venoms from N. kaouthia and N. oxiana, and poor reactivity towards 3FTxs and PLA2s. Moreover, there was considerable variation between antivenoms from different manufacturers. These data indicate that improvements to antivenom manufacturing in India are highly desirable.

KW - Biogeography

KW - Biodiversity

KW - venom variation

KW - snakebite

KW - neutralization

KW - antivenomics

KW - Naja naja

KW - Naja kaouthia

KW - Naja oxiana

U2 - https://doi.org/10.3390/toxins15040258

DO - https://doi.org/10.3390/toxins15040258

M3 - Article

VL - 15

JO - Toxins

JF - Toxins

SN - 2072-6651

IS - 4

ER -