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Fulltext Cross neutralization of Afro-Asian cobra and Asian krait venoms by a Thai polyvalent snake antivenom (Neuro Polyvalent Snake Antivenom)

Leong PK, Sim SM, Fung SY, Sumana K, Sitprija V, Tan NH

PLoS Negl Trop Dis, 2012;6(6):e1672.
PMID: 22679522 DOI: 10.1371/journal.pntd.0001672

BACKGROUND: Snake 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/SIGNIFICANCE: The 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.

Matched MeSH terms: Cross Protection*
Cross neutralization of common Southeast Asian viperid venoms by a Thai polyvalent snake antivenom (Hemato Polyvalent Snake Antivenom)

Leong PK, Tan CH, Sim SM, Fung SY, Sumana K, Sitprija V, et al.

Acta Trop, 2014 Apr;132:7-14.
PMID: 24384454 DOI: 10.1016/j.actatropica.2013.12.015

Snake envenomation is a serious public health threat in many rural areas of Asia and Africa. Antivenom has hitherto been the definite treatment for snake envenomation. Owing to a lack of local production of specific antivenom, most countries in these regions fully depend on foreign supplies of antivenoms. Often, the effectiveness of the imported antivenoms against local medically important species has not been validated. This study aimed to assess cross-neutralizing capacity of a recently developed polyvalent antivenom, Hemato Polyvalent Snake Antivenom (HPAV), against venoms of a common viper and some pit vipers from Southeast Asia. Neutralisation assays showed that HPAV was able to effectively neutralize lethality of the common Southeast Asian viperid venoms examined (Calloselasma, Crytelytrops, Popeia, and Daboia sp.) except for Tropidolaemus wagleri venom. HPAV also effectively neutralized the procoagulant and hemorrhagic activities of all the venoms examined, corroboratively supporting the capability of HPAV in neutralizing viperid venoms which are principally hematoxic. The study also indicated that HPAV fully prevented the occurrence of hematuria and proteinuria in mice envenomed with Thai Daboia siamensis venom but was only partially effective against venoms of Myanmar D. siamensis. Thus, HPAV appears to be useful against its homologous venoms and venoms from Southeast Asian viperids including several medically important pit vipers belonging to the Trimeresurus complex. Nevertheless, the effectiveness of HPAV as a paraspecific antivenom for treatment of viperid envenomation in Southeast Asian region requires further assessment from future clinical trials.

Matched MeSH terms: Cross Protection*
Fulltext Universal oral vaccine for influenza infections

Yap, Wei Boon, Toong, Seng Tan, Sharifah Syed Hassan, Jeffrey Cheah

Jurnal Sains Kesihatan Malaysia, 2018;16(2):51-64.
MyJurnal

Each year, influenza A infections have caused tremendous death rate as high as 300,000-500,000 globally. Although
there are effective anti-influenza agents and vaccines, high mutational rate among influenza A viruses renders dramatic
decline in the effectiveness of anti-influenza agents or vaccines in certain individuals. The situation is further complicated
by limitations in influenza vaccine production, for instance, long production period, limited vaccine capacity and lack
of cross-protection against various influenza A virus strains. To solve these issues, development of universal influenza
vaccine based on conserved antigens such as non-stuctural protein 1 (NS1) has been endeavoured. NS1 protein is highly
conserved in all influenza A virus strains known by far, produced abundantly on infected cell surfaces and responsible for
maintaining virulence. Furthermore, cytotoxic T-lymphocytes that are active against NS1 were also reported to be able
to avoid shedding of influenza in hosts. To better inhibit influenza infections, oral immunization has long been proposed
due to feasibility of this method to be implemented and safer for recipients while able to target influenza A viruses from
the entry point. Lactobacillus has been vastly studied for its roles as bacterial carrier in oral vaccine development due
to its significant probiotic properties. For examples, stimulation of immune responses in oral and airway mucosal layers,
high colonization in oral and airway mucosal layers and great natural adjuvant effects. In this light, influenza universal
oral vaccine developed using NS1 dan Lactobacillus should be further studied in influenza oral vaccine design.

Matched MeSH terms: Cross Protection
Fulltext Multi-Epitope Peptide-Based and Vaccinia-Based Universal Influenza Vaccine Candidates Subjected to Clinical Trials

Romeli S, Hassan SS, Yap WB

Malays J Med Sci, 2020 Mar;27(2):10-20.
PMID: 32788837 DOI: 10.21315/mjms2020.27.2.2

In light of the limited protection conferred by current influenza vaccines, immunisation using universal influenza vaccines has been proposed for protection against all or most influenza sub-types. The fundamental principle of universal influenza vaccines is based on conserved antigens found in most influenza strains, such as matrix 2, nucleocapsid, matrix 1 and stem of hemagglutinin proteins. These antigens trigger cross-protective immunity against different influenza strains. Many researchers have attempted to produce the conserved epitopes of these antigens in the form of peptides in the hope of generating universal influenza vaccine candidates that can broadly induce cross-reactive protection against influenza viral infections. However, peptide vaccines are poorly immunogenic when applied individually owing to their small molecular sizes. Hence, strategies, such as combining peptides as multi-epitope vaccines or presenting peptides on vaccinia virus particles, are employed. This review discusses the clinical and laboratory findings of several multi-epitope peptide vaccine candidates and vaccinia-based peptide vaccines. The majority of these vaccine candidates have reached the clinical trial phase. The findings in this study will indeed shed light on the applicability of universal influenza vaccines to prevent seasonal and pandemic influenza outbreaks in the near future.

Matched MeSH terms: Cross Protection
Fulltext Implications of a highly divergent dengue virus strain for cross-neutralization, protection, and vaccine immunity

Chen RE, Smith BK, Errico JM, Gordon DN, Winkler ES, VanBlargan LA, et al.

Cell Host Microbe, 2021 Nov 10;29(11):1634-1648.e5.
PMID: 34610295 DOI: 10.1016/j.chom.2021.09.006

Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1-4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.

Matched MeSH terms: Cross Protection*
Fulltext Elucidating the Efficacy of Vaccination against Vibriosis in Lates calcarifer Using Two Recombinant Protein Vaccines Containing the Outer Membrane Protein K (r-OmpK) of Vibrio alginolyticus and the DNA Chaperone J (r-DnaJ) of Vibrio harveyi

Silvaraj S, Md Yasin IS, A Karim MM, Saad MZ

Vaccines (Basel), 2020 Nov 06;8(4).
PMID: 33171991 DOI: 10.3390/vaccines8040660

Recombinant cell vaccines expressing the OmpK and DnaJ of Vibrio were developed and subsequently, a vaccination efficacy trial was carried out on juvenile seabass (~5 cm; ~20 g). The fish were divided into 5 groups of 50 fish per group, kept in triplicate. Groups 1 and 2 were injected with 107 CFU/mL of the inactivated recombinant cells vaccines, the pET-32/LIC-OmpK and pET-32/LIC-DnaJ, respectively. Group 3 was similarly injected with 107 CFU/mL of inactivated E. coli BL21 (DE3), Group 4 with 107 CFU/mL of formalin killed whole cells V. harveyi, and Group 5 with PBS solution. Serum, mucus, and gut lavage were used to determine the antibody levels before all fish were challenged with V. harveyi, V. alginolyticus, and V. parahemolyticus, respectively on day 15 post-vaccination. There was significant increase in the serum and gut lavage antibody titers in the juvenile seabass vaccinated with r-OmpK vaccine. In addition, there was an up-regulation for TLR2, MyD88, and MHCI genes in the kidney and intestinal tissues of r-OmpK vaccinated fish. At the same time, r-OmpK triggered higher expression level of interleukin IL-10, IL-8, IL-1ß in the spleen, intestine, and kidney compared to r-DnaJ. Overall, r-OmpK and r-DnaJ triggered protection by curbing inflammation and strengthening the adaptive immune response. Vaccinated fish also demonstrated strong cross protection against heterologous of Vibrio isolates, the V. harveyi, V. alginolyticus, and V. parahaemolyticus. The fish vaccinated with r-OmpK protein were completely protected with a relative per cent of survival (RPS) of 90 percent against V. harveyi and 100 percent against V. alginolyticus and V. parahaemolyticus. A semi-quantitative PCR detection of Vibrio spp. from the seawater containing the seabass also revealed that vaccination resulted in reduction of pathogen shedding. In conclusion, our results suggest r-OmpK as a candidate vaccine molecule against multiple Vibrio strain to prevent vibriosis in marine fish.

Matched MeSH terms: Cross Protection
Fulltext Formaldehyde-inactivated whole-virus vaccine protects a murine model of enterovirus 71 encephalomyelitis against disease

Ong KC, Devi S, Cardosa MJ, Wong KT

J Virol, 2010 Jan;84(1):661-5.
PMID: 19864378 DOI: 10.1128/JVI.00999-09

Enterovirus 71 (EV71) causes childhood hand, foot, and mouth disease and neurological complications, and no vaccines or therapeutic drugs are currently available. Formaldehyde-inactivated whole-virus vaccines derived from EV71 clinical isolates and a mouse-adapted virus (MAV) were tested in a mouse model of EV71 encephalomyelitis. After only two immunizations, given to mice at 1 and 7 days of age, the MAV vaccine protected mice at 14 days of age from disease. Tissues from immunized mice were negative for virus by viral culture, reverse transcriptase PCR, immunohistochemistry analysis, and in situ hybridization. Cross-neutralizing EV71 antibodies to strains with genotypes B3, B4, and C1 to C5 generated in immunized adult mice were able to passively protect 14-day-old mice from disease.

Matched MeSH terms: Cross Protection
Fulltext Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study

Hss AS, Koh MT, Tan KK, Chan LG, Zhou L, Bouckenooghe A, et al.

Vaccine, 2013 Dec 2;31(49):5814-21.
PMID: 24135573 DOI: 10.1016/j.vaccine.2013.10.013

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia.

Matched MeSH terms: Cross Protection
Fulltext Cellular immune responses to recurring influenza strains have limited boosting ability and limited cross-reactivity to other strains

Keynan Y, Card CM, Ball BT, Li Y, Plummer FA, Fowke KR

Clin Microbiol Infect, 2010 Aug;16(8):1179-86.
PMID: 20670292 DOI: 10.1111/j.1469-0691.2010.03142.x

Influenza vaccine provides protection against infection with matched strains, and this protection correlates with serum antibody titres. In addition to antibodies, influenza-specific CD8+ T-lymphocyte responses are important in decreasing disease severity and facilitating viral clearance. Because this response is directed at internal, relatively conserved antigens, it affords some cross-protection within a given subtype of influenza virus. With the possibility of a broader A(H1N1) Mexico outbreak in the fall of 2009, it appeared worthwhile studying the degree of cellular immune response-mediated cross-reactivity among influenza virus isolates. The composition of the 2006-2007 influenza vaccine included the A/New Caledonia/20/1999 strain (comprising a virus that has been circulating, and was included in vaccine preparations, for 6-7 years) and two strains not previously included (Wisconsin and Malaysia). This combination afforded us the opportunity to determine the degree of cross-reactive cellular immunity after exposure to new viral strains. We analysed the antibody responses and the phenotype and function of the T cell response to vaccine components. The results obtained show that antibody responses to A/New-Caledonia were already high and vaccination did not increase antibody or cytotoxic T lymphocyte responses. These data suggest that repeated exposure to the same influenza stain results in limited boosting of humoral and cellular immune responses.

Matched MeSH terms: Cross Protection
Fulltext Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations

Liu L, Mo Z, Liang Z, Zhang Y, Li R, Ong KC, et al.

BMC Med, 2015;13:226.
PMID: 26381232 DOI: 10.1186/s12916-015-0448-7

To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy.

Matched MeSH terms: Cross Protection
Fulltext Protection against henipaviruses in swine requires both, cell-mediated and humoral immune response

Pickering BS, Hardham JM, Smith G, Weingartl ET, Dominowski PJ, Foss DL, et al.

Vaccine, 2016 09 14;34(40):4777-86.
PMID: 27544586 DOI: 10.1016/j.vaccine.2016.08.028

Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was not detected, and the animals were only partially protected against challenge with 5×10(5) PFU of HeV per animal. In the second group, cross-neutralizing antibody levels against NiV in the sGHEV vaccinated animals did not reach protective levels, and with no activation of cellular immune memory, these animals were not protected against NiV. Only pigs orally infected with 5×10(4) PFU of NiV per animal were protected against nasal challenge with 5×10(5) PFU of NiV per animal. This group of pigs developed protective antibody levels, as well as cell-mediated immune memory. Peripheral blood mononuclear cells restimulated with UV-inactivated NiV upregulated IFN-gamma, IL-10 and the CD25 activation marker on CD4(+)CD8(+) T memory helper cells and to lesser extent on CD4(-)CD8(+) T cells. In conclusion, both humoral and cellular immune responses were required for protection of swine against henipaviruses.

Matched MeSH terms: Cross Protection
Fulltext Development and immunogenic potentials of chitosan-saponin encapsulated DNA vaccine against avian infectious bronchitis coronavirus

Bande F, Arshad SS, Bejo MH, Omar AR, Moeini H, Khadkodaei S, et al.

Microb Pathog, 2020 Dec;149:104560.
PMID: 33068733 DOI: 10.1016/j.micpath.2020.104560

Infectious Bronchitis (IB) is an economically important avian disease that considerably threatens the global poultry industry. This is partly, as a result of its negative consequences on egg production, weight gain as well as mortality rate.The disease is caused by a constantly evolving avian infectious bronchitis virus whose isolates are classified into several serotypes and genotypes that demonstrate little or no cross protection. In order to curb the menace of the disease therefore, broad based vaccines are urgently needed. The aim of this study was to develop a recombinant DNA vaccine candidate for improved protection of avian infectious bronchitis in poultry. Using bioinformatics and molecular cloning procedures, sets of monovalent and bivalent DNA vaccine constructs were developed based on the S1 glycoprotein from classical and variants IBV strains namely, M41 and CR88 respectively. The candidate vaccine was then encapsulated with a chitosan and saponin formulated nanoparticle for enhanced immunogenicity and protective capacity. RT-PCR assay and IFAT were used to confirm the transcriptional and translational expression of the encoded proteins respectively, while ELISA and Flow-cytometry were used to evaluate the immunogenicity of the candidate vaccine following immunization of various SPF chicken groups (A-F). Furthermore, histopathological changes and virus shedding were determined by quantitative realtime PCR assay and lesion scoring procedure respectively following challenge of various subgroups with respective wild-type IBV viruses. Results obtained from this study showed that, groups vaccinated with a bivalent DNA vaccine construct (pBudCR88-S1/M41-S1) had a significant increase in anti-IBV antibodies, CD3+ and CD8+ T-cells responses as compared to non-vaccinated groups. Likewise, the bivalent vaccine candidate significantly decreased the oropharyngeal and cloacal virus shedding (p < 0.05) compared to non-vaccinated control. Chickens immunized with the bivalent vaccine also exhibited milder clinical signs as well as low tracheal and kidney lesion scores following virus challenge when compared to control groups. Collectively, the present study demonstrated that bivalent DNA vaccine co-expressing dual S1 glycoprotein induced strong immune responses capable of protecting chickens against infection with both M41 and CR88 IBV strains. Moreso, it was evident that encapsulation of the vaccine with chitosan-saponin nanoparticle further enhanced immune responses and abrogates the need for multiple booster administration of vaccine. Therefore, the bivalent DNA vaccine could serve as efficient and effective alternative strategy for the control of IB in poultry.

Matched MeSH terms: Cross Protection

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