Cross Neutralization of Afro-Asian Cobra and Asian Krait Venoms by a Thai Polyvalent Snake Antivenom (Neuro Polyvalent Snake Antivenom)

Abstract

BackgroundSnake envenomation is a serious public health threat in the rural areas of Asian and African countries. To date, the only proven treatment for snake envenomation is antivenom therapy. Cross-neutralization of heterologous venoms by antivenom raised against venoms of closely related species has been reported. The present study examined the cross neutralizing potential of a newly developed polyvalent antivenom, termed Neuro Polyvalent Snake Antivenom (NPAV). NPAV was produced by immunization against 4 Thai elapid venoms.Principal Findings In vitro neutralization study using mice showed that NPAV was able to neutralize effectively the lethality of venoms of most common Asiatic cobras (Naja spp.), Ophiophagus hannah and kraits (Bungarus spp.) from Southeast Asia, but only moderately to weakly effective against venoms of Naja from India subcontinent and Africa. Studies with several venoms showed that the in vivo neutralization potency of the NPAV was comparable to the in vitro neutralization potency. NPAV could also fully protect against N. sputatrix venom-induced cardio-respiratory depressant and neuromuscular blocking effects in anesthetized rats, demonstrating that the NPAV could neutralize most of the major lethal toxins in the Naja venom.Conclusions/SignificanceThe newly developed polyvalent antivenom NPAV may find potential application in the treatment of elapid bites in Southeast Asia, especially Malaysia, a neighboring nation of Thailand. Nevertheless, the applicability of NPAV in the treatment of cobra and krait envenomations in Southeast Asian victims needs to be confirmed by clinical trials. The cross-neutralization results may contribute to the design of broad-spectrum polyvalent antivenom.

Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization

“…31 Surprisingly, the venoms of N. naja from India and Sri Lanka were noted to be less neurotoxic with higher LD 50 values, 31 approximately 5-10 times that of the Pakistani species revealed in this study. This is supported by the venom profiling where α-NTXs (with LD 50 values of 0.07-0.18 μg/g) made up nearly 40% abundance of the Pakistani N. naja venom, comparable to that found in the Thai monocled cobra.…”

“…This might be partly due to the inferior quality of the said antivenom, for instance, in terms of its lower protein (antibody) content and potency, as shown in another report. 31 Results from the current study on the moderate efficacy of VPAV indicate that there is similar toxin antigenicity in both the venoms from Indian and Pakistani species, despite the variation noted in the relative abundance of their NTXs. As we extended the cross-neutralization study involving heterologous antivenoms indicated for N. kaouthia (NKMAV) and N. atra (NBAV), it is evident that NKMAV, with its relatively higher potency (twice that of VPAV), is perhaps the antivenom with the right formulation to neutralize venom that has high NTXs content, in particular the LNTX subtypes that are abundant in the venoms of Thai N. kaouthia and Pakistani N. naja.…”

Immunological cross-reactivity and neutralization of the principal toxins of Naja sumatrana and related cobra venoms by a Thai polyvalent antivenom (Neuro Polyvalent Snake Antivenom)

“…The survival ratio was recorded after 48 h to determine the LD 50 (Ramos-Cerrillo et al, 2008). Values for crude venoms of N. sumatrana, N. kaouthia and N. sputatrix were referred to the previous data reported from the same laboratory (Leong et al, 2012a).…”

“…However, if 200 L of the reconstituted antivenom (maximum permitted volume to inject into the mouse) failed to give full protection of the mice, a lower challenge dose of 1.5 LD 50 was used instead. Values of neutralization efficacy for crude venoms of N. sumatrana, N. kaouthia and N. sputatrix were referred to the previous data reported from the same laboratory (Leong et al, 2012a).…”

“…Cross-neutralization of Naja venoms by heterologous antivenom is a well-known phenomemon (Cham et al, 2013;Kornhauser et al, 2013;Leong et al, 2012a). Neuro Polyvalent Snake Antivenom (NPAV) (produced against the venoms of the Thai monocled cobra, Naja kaouthia, and three other Thai elapid snakes) was chosen for this study as it is a commonly used polyvalent antivenom in Thailand and Malaysia, and extensive cross-neutralization data of this antivenom against venoms from various cobras are available for comparison purpose (Leong et al, 2012a). This study investigated the immunoreactivity and neutralization profiles of NPAV against various principal toxins of Naja sumatrana (Equatorial spitting cobra), Naja kaouthia (Monocled cobra) and Naja sputatrix (Javen spitting cobra) venoms.…”