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Antiviral Research (v.95, #3)

Inside Back Cover: Notes to Authors (pp. ibc).

Prelim II: Editorial Board (pp. ii).

Rhinovirus infections and immunisation induce cross-serotype reactive antibodies to VP1 by Gary R. McLean; Ross P. Walton; Shweta Shetty; Nasren Paktiawal; Tatiana Kebadze; Leila Gogsadze; Katarzyna Niespodziana; Rudolf Valenta; Nathan W. Bartlett; Sebastian L. Johnston (pp. 193-201).

► Antibody responses in mouse models of intranasal RV infection and immunisation. ► RV infection induces cross-serotype RV-specific IgG responses. ► RV capsid protein VP1 was the dominant antibody target. ► Induction of neutralising antibodies requires two RV infections. ► RV immunisation generates cross-serotype neutralising antibodies.Rhinoviruses (RVs) are ubiquitous human respiratory viruses, the major cause of common colds, acute exacerbations of asthma and other respiratory diseases. The development of antibodies to RV following primary infection is poorly understood and there is currently no RV vaccine available. We therefore used mouse models of intranasal RV infection and immunisation to determine the induction, magnitude and specificity of antibody responses. Strong cross-serotype RV-specific IgG responses in serum and bronchoalveolar lavage were induced towards the RV capsid protein VP1. IgA responses were weaker, requiring two infections to generate detectable RV-specific binding. Similarly two or more RV infections were necessary to induce neutralising antibodies. Immunisation strategies boosted homotypic as well as inducing cross-serotype neutralising IgG responses. We conclude that VP1 based antigens combined with adjuvants may permit successful antibody-mediated vaccine design and development.

Keywords: Antibodies; Rhinovirus; Vaccine; Mouse model

Nuclear trafficking of proteins from RNA viruses: Potential target for antivirals? by Leon Caly; Kylie M. Wagstaff; David A. Jans (pp. 202-206).

► Many RNA viruses that replicate in the cytoplasm require the nuclear transport of one or more proteins. ► Blocking the transport of these components into or out of the nucleus can reduce viral replication. ► Inhibition of nuclear trafficking of RNA viral proteins represents a novel antiviral strategy. ► Targeting the interface between viral and host cell proteins should improve drug specificity without toxicity.A key aspect of the infectious cycle of many viruses is the transport of specific viral proteins into the host cell nucleus to perturb the antiviral response. Examples include a number of RNA viruses that are significant human pathogens, such as human immunodeficiency virus (HIV)-1, influenza A, dengue, respiratory syncytial virus and rabies, as well agents that predominantly infect livestock, such as Rift valley fever virus and Venezuelan equine encephalitis virus. Inhibiting the nuclear trafficking of viral proteins as a therapeutic strategy offers an attractive possibility, with important recent progress having been made with respect to HIV-1 and dengue. The results validate nuclear protein import as an antiviral target, and suggest the identification and development of nuclear transport inhibitors as a viable therapeutic approach for a range of human and zoonotic pathogenic viruses.

Keywords: Nuclear transport; HIV integrase; Influenza A NP; Dengue virus NS5; Respiratory syncytial virus matrix; Rift valley fever virus NSs; Venezuelan equine encephalitis virus; Ivermectin

Patients on a combined antiretroviral therapy after maraviroc clinical test show no immunovirological impairment by Miguel Genebat; Ildefonso Pulido; M. Concepción Romero-Sánchez; Alejandro González-Serna; Sara Ferrando-Martínez; Kawthar Machmach; Yolanda M. Pacheco; Mª Ángeles Muñoz-Fernández; Ezequiel Ruiz-Mateos; Manuel Leal (pp. 207-211).

► Maraviroc clinical test (MCT) as a method to select candidate patients to be treated with CCR5-antagonists. ► Advantages of MCT compared with other tropism assays. ► Long-term outcome of patients starting cART after MCT shows immunovirological efficacy. ► Tropism analysis during MCT shows no clinically relevant tropism change after short-term maraviroc monotherapy.The maraviroc clinical test (MCT) is a clinical approach to establish the indication of maraviroc treatment. In this study, we analysed the long-term outcome of patients receiving a combined antiretroviral therapy (cART) selected according to MCT results. Ninety-two consecutive HIV-infected patients underwent MCT. A virological response (<40 HIV-RNA copies/ml after 24weeks) was observed in 76/92 patients (82.6%). These patients ( n=76) were included in a time to treatment failure analysis; after a mean follow-up period of 88weeks, treatment failure was confirmed in 14 patients (18.4%). Tropism switch during MCT was observed in 3/35 patients (8.6%); these patients experienced excellent long-term outcome on cART. In conclusion, MCT should be considered as an additional method before CCR5-antagonists prescription.

Keywords: Abbreviations; MVC; maraviroc; MCT; maraviroc clinical test; cART; CXCR4 (X4), combined antirretroviral therapy; D/M; dual/mixedAntiretroviral therapy; Maraviroc; HIV tropism; CCR5

HIV-coinfection leads to a modest increase in plasma HCV-RNA load in patients with chronic HCV infection by Karin Neukam; Silvia García-Rey; Celia Cifuentes; Juan Macías; José A Mira; María J Vázquez; Manuel Parra-Sánchez; José C Palomares; Nicolás Merchante; Federico A Di Lello; Juan A Pineda (pp. 212-215).

► The influence of HIV coinfection on HCV RNA load has been evaluated. ► A total of 396 HCV-monoinfected and 467 HIV/HCV-coinfected patients were included. ► HIV coinfection leads to a mild increase in plasma HCV RNA burden. ► The magnitudes of the differences are low and can be counterbalanced with antiviral therapy. ► Contribution to lower anti-HCV therapy response rates in coinfection is questionable.The influence of HIV coinfection on plasma hepatitis C virus (HCV) RNA load has not been reliably evaluated. We analyzed plasma HCV RNA load in 396 HCV-monoinfected and 467 HIV/HCV-coinfected patients. Median HCV RNA concentrations (interquartile range) in HCV-monoinfected patients were 5.88 (5.3–6.2) log₁₀IU/mL versus 5.96 (5.6–6.5) log₁₀IU/mL in HIV/HCV-coinfected individuals ( p=0.033) as determined with the Cobas Amplicor Test and 6.06 (5.4–5.7) log₁₀IU/mL versus 6.3 (5.5–6.9) log₁₀IU/mL ( p=0.026) using the Cobas TaqMan System. The plasma HCV RNA load in patients with HIV infection and undetectable plasmatic HIV RNA was similar to that observed in HCV-monoinfected individuals [6.02 (5.45–6.61) log₁₀IU/mL versus 6.01 (5.36–6.59) log₁₀IU/mL, respectively ( p=1.0)]. In conclusion, HIV coinfection tends to be associated with higher plasma HCV RNA load, however, the magnitude of the differences is small and this effect can be counterbalanced with antiviral therapy.

Keywords: Abbreviations; DL; detection limit; HCV; hepatitis C virus; Peg-IFN; pegylated interferon; RBV; ribavirin; SVR; sustained virologic responseHepatitis C virus; HIV; RNA load; Pegylated interferon; Ribavirin; Polymerase chain reaction

Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1 by Gang Zou; Petra Kukkaro; Shee-Mei Lok; Jowin K.W. Ng; Grace K. Tan; Brendon J. Hanson; Sylvie Alonso; Paul A. MacAry; Pei-Yong Shi (pp. 216-223).

► We report the resistance profile of DENV-1 against HM14c10 in cell culture. ► Envelope T51K mutation completely abolished the antibody binding to the DENV-1 virion. ► Envelope T51K mutation could not be neutralized by HM14c10 in vitro or in vivo. ► We examine the effect of envelope T51K mutation in vitro and in vivo.The four serotypes of dengue virus (DENV) are the causative agents of the most prevalent mosquito-borne viral disease in human. No clinically approved antiviral therapy is currently available. Therapeutic antibodies represent a viable approach for potential treatment of DENV infection. We recently isolated a human monoclonal antibody (HM14c10) that selectively neutralizes DENV serotype 1 (DENV-1), but not serotypes 2, 3, and 4. Here we report the resistance profile of DENV-1 against HM14c10 in cell culture. Escape mutant viruses readily emerged by culturing wild-type DENV-1 in the presence of the HM14c10 antibody. Sequencing of resistant viruses revealed a single T51K substitution in the domain I/II hinge region of the viral envelope protein. Residue T51 is located within the HM14c10 epitope and is highly conserved among various DENV-1 isolates. Recombinant DENV-1 containing the T51K mutation could not be neutralized by HM14c10 in vitro or in vivo. Biochemical assay revealed that the T51K mutation completely abolished the antibody binding to the DENV-1 virion. Collectively, the results demonstrate that a single amino acid change in DENV envelope protein can confer resistance to a potent antibody through abolishing the antibody-virus interaction.

Keywords: Dengue virus; Neutralizing antibody; Escape mutant; Virus entry; Flavivirus envelope protein

Effects of mutations on herpes simplex virus 1 thymidine kinase functionality: An in vitro assay based on detection of monophosphate forms of acyclovir and thymidine using HPLC/DAD by Nicolas Malartre; Roselyne Boulieu; Nisrine Falah; Jean-Claude Cortay; Bruno Lina; Florence Morfin; Emilie Frobert (pp. 224-228).

► A non-isotopic method to assess TK activity using ACV and dT as substrates. ► Dosage of monophosphate forms of both ACV and dT using HPLC/DAD. ► Phenotypes of TKs characterized as TK altered, TK deficient or TK partial. ► Database of UL23 TK gene completed with six novel mutations. ► Importance for fast and efficient HSV genotyping.Discrimination between the mutations responsible for drug resistance and those of UL23 TK gene polymorphism can be difficult. A non-isotopic method has been developed to assess TK functionality by measuring monophosphate forms of both acyclovir (ACV) and thymidine using HPLC/DAD. Phenotypes of TKs could thus be characterized as TK altered (P84L, A189V, L227F), TK deficient (G200S, L291P) or TK partial (R163H). A reliable link between HSV UL23 TK mutations and ACV resistance is necessary for developing a powerful genotyping tool to detect ACV resistance quickly in clinical samples.

Keywords: HSV1; Thymidine kinase; ACV resistance; HPLC/DAD; Genotyping

Influenza virosome/DNA vaccine complex as a new formulation to induce intra-subtypic protection against influenza virus challenge by Masoumeh Tavassoti Kheiri; Abbas Jamali; Mohammad Shenagari; Hamidreza Hashemi; Farzaneh Sabahi; Fatemeh Atyabi; Reza Saghiri (pp. 229-236).

Influenza virosome is one of the commercially available vaccines that have been used for a number of years. Like other influenza vaccines, the efficacy of the virosomal vaccine is significantly compromised when circulating viruses do not have a good match with vaccine strains due to antigenic drift or less frequent emergence of a pandemic virus. A major advantage of virosome over other influenza vaccine platforms is its intrinsic adjuvant activity and potential carrier capability which have been exploited in this study to broaden vaccine protectivity by incorporating a conserved component of influenza virus in seasonal vaccine formulation. Influenza nucleoprotein (NP)-encoding plasmid was adsorbed onto surface of influenza virosomes as a virosome/DNA vaccine complex. Mice were immunized with a single dose of the influenza virosome attached with the NP plasmid or NP plasmid alone where both influenza virosomes and NP gene were derived from influenza A virus H1N1 New/Caledonia strain. Analysis of the cellular immune responses showed that 5μg (10-fold reduced dose) of the NP plasmid attached to the virosomes induced T cell responses equivalent to those elicited by 50μg of NP plasmid alone as assessed by IFN-γ and granzyme B ELISPOT. Furthermore, the influenza virosome/NP plasmid complex protected mice against intra-subtypic challenge with the mouse adapted H1N1 PR8 virus, while mice immunized with the virosome alone did not survive. Results of hemagglutination inhibition test showed that the observed intra-subtypic cross-protection could not be attributed to neutralizing antibodies. These findings suggest that influenza virosomes could be equipped with an NP-encoding plasmid in a dose-sparing fashion to elicit anti-influenza cytotoxic immune responses and broaden the vaccine coverage against antigenic drift.

Keywords: Virosomal influenza vaccine; Virosome/DNA complex; Nucleoprotein; Antigenic drift

Inhibition of canine parvovirus replication in cultured cells by small interfering RNAs expressed from plasmid vectors by Ying He; Wangbin Cao; Sumin Pan; Fei Zhong; Manfu Zhang (pp. 237-241).

► Target specific siRNA expressed in cell lines decreased CPV infection. ► Target specific siRNA expressed in cell lines suppressed replication of CPV. ► A siRNA targeting CPV sequences shared by genes of NS1 and NS2 had high efficiency.Small interfering RNAs (siRNAs) target complementary mRNA for specific degradation, a mechanism many viruses are susceptible too. Thus, siRNA degradation of target RNAs can be exploited as novel therapeutics. In this report, we show that the vector-based siRNAs (psiSTRIKEs) expressed by a human U6 promoter could efficiently inhibit CPV replication in cell culture. A series of PsiSTRIKE vectors expressing siRNA were constructed that target structural protein genes or nonstructural protein genes of CPV genome. These plasmids were transfected into FK81 cells via lipofectin and the stable transfection clones were selected. The immunostaining, plaque assay, and cell proliferation assay of the cells infected by CPV were performed. The results show that siRNAs against nonstructural protein genes effectively inhibited CPV replication. The inhibition efficiencies detected by immunostaining assay of psiSTRIKE/vp1510, psiSTRIKE/NS160, and psiSTRIKE/NS1939 were 66%, 76% and 78%, respectively at 48h, and 69%, 46% and 67%, respectively at 96h. Plaque assay showed that, comprising to the control, the psiSTRIKE/NS160 reduced the virion production by 100-fold, and psiSTRIKE/NS1939 or psiSTRIKE/VP1510 reduced the virion production 13-fold. When compared to control, the viability of cells transfected psiSTRIKE/NS160 increased 78% and 124%, respectively at 72 and 120h. Our study may provide a potential therapy against CPV infection.

Keywords: Canine parvovirus; Replication; Small interfering RNAs

Is minocycline useful for therapy of acute viral encephalitis? by Alan C. Jackson (pp. 242-244).

► Minocycline has anti-inflammatory, anti-apoptotic, and anti-oxidant properties. ► Minocycline may be beneficial in some neurological diseases and harmful in others. ► Minocycline should not be used as empirical therapy for acute viral encephalitis. ► Further studies are needed to determine minocycline’s role in viral encephalitis.Minocyline is a tetracycline derivative with anti-inflammatory, anti-apoptotic, and anti-oxidant properties. Therapy has proved useful in some experimental models of both noninfectious and infectious neurological diseases and also in clinical trials in humans, including acute traumatic cervical spinal cord injury. In models of viral encephalitis, treatment has shown both beneficial and deleterious effects. In reovirus infection in mice, minocycline delayed the disease, but did not improve either the morbidity or mortality of the disease. In neuroadapted Sindbis virus infection of mice, minocycline prevented disease, but therapy needed to be given before clinical signs were present in most of the animals. In experimental rabies in neonatal mice minocycline aggravated the disease, likely related to anti-inflammatory effects. Minocycline has also been shown to aggravate disease in a mouse model of Huntington disease, in a monkey model of Parkinson disease, and in a mouse model of hypoxic-ischemic brain injury. Hence, there is experimental evidence of benefit of minocycline in both infectious and noninfectious neurological diseases, but there is a lack of benefit and harmful effects in other diseases. This may reflect multiple mechanisms of actions that cannot be predicted in a new disease or in an infection caused by a specific viral agent. Minocycline therapy is a double-edged sword and this drug should not be given empirically to patients with acute viral encephalitis for anticipated neuroprotective effects. Much more work needs to be done in experimental models in animals as well as in clinical trials. Because patient enrollment in clinical trials on acute viral encephalitis has proven to be difficult, funding will be a challenge.

Keywords: Minocycline; Viral encephalitis; Encephalomyelitis; Rabies; Rabies virus

Liver X receptors agonists impede hepatitis C virus infection in an Idol-dependent manner by Jing Zeng; Yang Wu; Qingjiao Liao; Lixia Li; Xinwen Chen; Xulin Chen (pp. 245-256).

► Liver X receptors control LDLR expression in Idol-dependent manner in Huh7.5.1 cells. ► Idol (inducible degrader of the LDLR) or LXR agonists can inhibit HCV infection. ► Idol or LXR agonists does not inhibit HCV replication in replicon system.Hepatitis C virus (HCV) is a major human pathogen that causes many serious diseases, including acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma. Treatments for this virus are inadequate, and improved antiviral therapies are necessary. Although the precise mechanisms regulating HCV entry into hepatic cells are still unknown, the low-density lipoprotein receptor (LDLR) has been shown to be essential for entry of infectious HCV particles. Liver X receptors (LXR) were recently reported to control LDLR expression through the regulation of the expression of the Idol (inducible degrader of the LDLR) protein, which could trigger the ubiquitination and degradation of LDLR. In this study, we analyzed the antiviral effect of Idol in vitro. The results demonstrated that Huh7.5.1 cells that exogenously expressed Idol were resistant to HCV infection. Next, the treatment of HCV-infected Huh7.5.1 cells with either synthetic LXR agonists (GW3965 or T0901317) or the natural LXR ligand 24(S),25-epoxycholesterol inhibited HCV infection in a dose-dependent manner. Furthermore, a combination of LXR agonists and HCV RNA replication inhibitors exerted additive effects against HCV, as revealed by isobologram analysis. In conclusion, our data indicate that molecules such as LXR agonists, which could stimulate the expression of Idol, represent a new class of potential anti-HCV compounds, and these compounds could be developed for therapeutic use against HCV infection, either as a monotherapy, or in combination with other anti-HCV drugs.

Keywords: Hepatitis C virus; Liver X receptors; Idol; Low-density lipoprotein receptor

Countermeasures against viral diseases of farmed fish by Frederick S.B. Kibenge; Marcos G. Godoy; Mark Fast; Samuel Workenhe; Molly J.T. Kibenge (pp. 257-281).

► We review emerging viral diseases of aquaculture and their protection and control. ► Wild fish act as pathogen reservoir for farmed fish because of lack of physical barrier. ► There are relatively few fish virus vaccines available commercially. ► Immunostimulants are used in feed to enhance innate immunity of fish against viral infection. ► Antiviral drugs have not yet found commercial use in aquaculture against viral diseases.Farmed fish provide an increasing fraction of the human food supply, and are of major economic importance in many countries. As in the case of terrestrial agriculture, bringing together large numbers of animals of a single species (i.e., monoculture) increases the risk of infectious disease outbreaks, including viral infections. Aquaculture, in which farmed fish are kept at high population densities in close proximity with wild fish reservoirs, is ideal for the emergence of wild-type pathogens that exist benignly in local wild fish and/or the spreading of aquatic pathogens to wild fish that enter into or come into close proximity with net cages and with fish escaping from them. This paper provides a general review for the nonspecialist of viral diseases of farmed fish and how they could be prevented or treated. It has five principal objectives: (1) to provide an update on the most important and emerging viral diseases of salmonid aquaculture; (2) to review general aspects of innate antiviral defense against virus infections in fish, including recent advances in antiviral signaling; (3) to discuss current principles and practices of vaccinating fish; (4) to review antiviral drugs that have activity against viruses of farmed fish, and current barriers to employing them in aquaculture; and (5) to discuss the growing use of “functional feeds” in salmonid aquaculture to mitigate viral diseases. In conclusion, despite the challenging aquatic environment, it is expected that well thought-out combinations of vaccination and immunostimulants and/or antiviral drugs could provide solid protection against viral diseases of farmed fish.

Keywords: Fish viruses; Viral hemorrhagic septicaemia; Infectious hematopoietic necrosis; Spring viremia of carp; Infectious salmon anaemia; Aquaculture

The Syrian hamster model of hantavirus pulmonary syndrome by David Safronetz; Hideki Ebihara; Heinz Feldmann; Jay W. Hooper (pp. 282-292).

► Provide an in-depth review of the current literature on the hamster model of HPS. ► Critically evaluate the model in the context of the FDA’s Animal Rule. ► Emphasize important areas of research which should be addressed using this model.Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS.

Keywords: Hantavirus pulmonary syndrome; Andes virus; Bunyavirus; Hamster; Animal model

Molecular biology and genetic diversity of Rift Valley fever virus by Tetsuro Ikegami (pp. 293-310).

► We summarize genetic diversity among Rift Valley fever virus isolates. ► We summarize reported diagnostic systems to detect Rift Valley fever virus RNA. ► Rift Valley fever virus is relatively homogeneous. ► Sensitive detection of Rift Valley fever virus RNA is feasible. ► Development of vaccines or antivirals for Rift Valley fever is essential.Rift Valley fever virus (RVFV), a member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever (RVF), a mosquito-borne disease of ruminant animals and humans. The generation of a large sequence database has facilitated studies of the evolution and spread of the virus. Bayesian analyses indicate that currently circulating strains of RVFV are descended from an ancestral species that emerged from a natural reservoir in Africa when large-scale cattle and sheep farming were introduced during the 19th century. Viruses descended from multiple lineages persist in that region, through infection of reservoir animals and vertical transmission in mosquitoes, emerging in years of heavy rainfall to cause epizootics and epidemics. On a number of occasions, viruses from these lineages have been transported outside the enzootic region through the movement of infected animals or mosquitoes, triggering outbreaks in countries such as Egypt, Saudi Arabia, Mauritania and Madagascar, where RVF had not previously been seen. Such viruses could potentially become established in their new environments through infection of wild and domestic ruminants and other animals and vertical transmission in local mosquito species. Despite their extensive geographic dispersion, all strains of RVFV remain closely related at the nucleotide and amino acid level. The high degree of conservation of genes encoding the virion surface glycoproteins suggests that a single vaccine should protect against all currently circulating RVFV strains. Similarly, preservation of the sequence of the RNA-dependent RNA polymerase across viral lineages implies that antiviral drugs targeting the enzyme should be effective against all strains. Researchers should be encouraged to collect additional RVFV isolates and perform whole-genome sequencing and phylogenetic analysis, so as to enhance our understanding of the continuing evolution of this important virus. This review forms part of a series of invited papers in Antiviral Research on the genetic diversity of emerging viruses.

Keywords: Rift Valley fever virus; Bunyavirus; Phlebovirus; Genetic diversity; Phylogenetics

Induction of protective immune responses against EV71 in mice by baculovirus encoding a novel expression cassette for capsid protein VP1 by Balraj Premanand; Tanja K. Kiener; Tao Meng; Yun Rui Tan; Qiang Jia; Vincent T.K. Chow; Jimmy Kwang (pp. 311-315).

► Surface display of VP1 is enhanced using this novel expression cassette. ► Bac-VP1 elicited neutralizing antibodies which showed cross-protective against EV71. ► Newborn mice are passively protected by antisera of vaccinated mice.EV71 is a major causative agent of hand, foot and mouth disease (HFMD) and is responsible for large outbreaks in various Asian Pacific countries. In the present study, we generated the recombinant baculovirus (Bac-VP1) encoding VP1 in a novel expression cassette. The transmembrane domain of hemagglutinin of the H3N2 influenza virus was included in the cassette as a minimal membrane anchor for VP1. The protective immunity of Bac-VP1 was investigated in a mouse model. The results showed that mice vaccinated with live Bac-VP1 had strong VP1 specific antibody responses. In an in vitro neutralization assay Bac-VP1 sera exhibited cross-neutralization against homologous and heterologous EV71 strains with a maximum titer of 1:512. Passive immunization studies confirmed that these sera were able to provide 100% protection against 5 MLD₅₀ of mouse adapted EV71 (B4 strain). This study revealed that baculovirus displaying VP1 with a HA transmembrane domain efficiently induced cross-neutralizing antibody responses in mice.

Keywords: Enterovirus 71 (EV71); Baculovirus surface display; VP1; HA transmembrane anchor; Immune responses

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Antiviral Research (v.95, #3)