Table of Contents

Volume 1, Issue 3

  May/June 2005

  Pages 93 - 128

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

A Tribute to Maurice Ralph Hilleman

Myron M. Levine and Robert C. Gallo
Pages 93 - 94
http://dx.doi.org/10.4161/hv.1.3.1967
Abstract | PDF

No abstract available.




REVIEW

Open Access Article

Towards an Epitope-Based Human Vaccine for Influenza

Tamar Ben-Yedidia and Ruth Arnon
Pages 95 - 101
http://dx.doi.org/10.4161/hv.1.3.1851
Abstract | PDF

The conventional, currently available vaccines against influenza virus, though quite successful, suffer from a few shortcomings; one major limitation is their restriction to the specific strains that are included in the vaccine. We review herewith some of the more recently developed influenza vaccines and further describe our own results on the design of epitope-based vaccine for human use. In this vaccine, a combination of B- and T-cell epitopes are individually expressed within an immunogenic molecule – salmonella flagellin - and the resultant recombinant flagella serve both as a carrier and as an adjuvant. The mixture of recombinant flagella expressing the appropriate epitopes was administered to young and aged mice as well as to human/mouse chimera model in which human PBMC are functioning within the mice body. Intranasal immunization in all these animal models led to effective protection against challenge infection with different strains of influenza virus.




RESEARCH PAPERS

Open Access Article

Poliovirus-Binding Inhibition ELISA for Evaluation of Immune Response to Oral Poliovirus Vaccine: A Possible Alternative to the Neutralization Test

A.P. Ivanov, E.M. Dragunsky, O.E. Ivanova, G.V. Rezapkin, S.G. Potapova and K.M. Chumakov
Pages 102 - 105
http://dx.doi.org/10.4161/hv.1.3.1719
Abstract | PDF

This study describes an ELISA variant (Binding Inhibition ELISA, BI ELISA) for the quantitative determination of neutralization-relevant antibodies to polioviruses. The test differs from previously described analogs by utilizing polyclonal immune reagents: capture antibodies and biotin-labeled detecting antibodies. The BI ELISA was compared with the conventional neutralization test (NT) by testing live Sabin and wild-type poliovirus strains. The comparison of 68 serum samples taken from Oral Poliovirus Vaccine (OPV) recipients showed 100 % specificity and sensitivity for Sabin 1 and Sabin 2, and 100 % sensitivity and 97 % specificity for Sabin 3. Good correlations (r = 0.7, 0.77, 0.65 for Sabin 1, 2, 3, respectively) were demonstrated between the NT and BI ELISA results. These results indicate that the BI ELISA can be used as a reliable alternative to the NT for determination of neutralization-relevant antibodies to polioviruses in vaccinees and in large-scale sero-epidemiological studies.

Open Access Article

Cutaneous Delivery of a Live, Attenuated Chimeric Flavivirus Vaccines against Japanese Encephalitis (ChimeriVaxTM-JE) in Non-Human Primates

Cheryl H. Dean, Jason B. Alarcon, Andrea M. Waterston, Ken Draper, Richard Early, Farshad Guirakhoo, Thomas P. Monath and John A. Mikszta
Pages 106 - 111
http://dx.doi.org/10.4161/hv.1.3.1797
Abstract | PDF

Flaviviral diseases such as yellow fever, Japanese encephalitis (JE) and dengue hemorrhagic fever cause enormous morbidity and mortality worldwide. There is an urgent need for alternative technologies for mass vaccination against these and other diseases, particularly in the developing world. Here, we administered a live attenuated, chimeric JE vaccine (ChimeriVaxTM-JE) to non-human primates by skin microabrasion and intradermal delivery using microneedles. Both cutaneous delivery methods induced mild viremia similar in magnitude to that observed following subcutaneous (SC) injection. The duration of viremia induced by cutaneous delivery (5-7 days), however, was substantially longer than via SC (0-3 days). In addition, mean neutralizing antibody titers in cutaneous delivery groups were up to 7-fold greater than via SC injection. There were no safety issues identified and both cutaneous delivery methods appeared to be well tolerated. Thus, cutaneous delivery may represent a minimally-invasive alternative approach for flavivirus vaccines that more closely resembles the natural route of viral infection.

Open Access Article

Lot-to-Lot Consistency of a Combined Hexavalent Diptheria-Tentanus-Acellular-Pertussis, Hepatitis B, Inactivated Polio and Haemophilus b Conjugate Vaccine, Adminstered to Healthy Chilean Infants at 2, 4 and 6 Months of Age

Rosanna Lagos, Agnès Hoffenbach, Michel Scemama, Martin Dupuy, Florian Schödel, Luc Hessel and Myron Levine
Pages 112 - 117
http://dx.doi.org/10.4161/hv.1.3.1848
Abstract | PDF

Objectives: To assess the safety, immunogenicity and lot consistency of a liquid hexavalent combined vaccine (DTaP-IPV-PRP~T-HBs, HEXAVAC®) (Sanofi-Pasteur MSD, France) administered to infants at 2, 4, and 6 months of age. Methods: A total of 1028 infants were vaccinated with one of 3 vaccine lots, in a randomized, double-blind fashion. Equivalence testing was used to compare post-vaccination seroprotection/seroconversion rates and geometric mean titers (GMTs) for each antigen between the three lots. Blood samples were drawn before vaccination and one month after the third dose. Local and systemic adverse events were monitored for 3 days following each injection. Results: Equivalence between lots was demonstrated for all antigens, on post-dose 3 seroprotection/seroconversion rates and GMTs. Reported rates of local and systemic adverse events tended to increase with subsequent doses. Altogether, 11.8% of the infants reported at least one adverse local event (mainly redness and induration/swelling) after the first dose and 36.1% after the third dose. Systemic adverse events (mainly irritability and fever) were reported by 39.2% of the infants after the first dose and by 57.5% after the third one. Conclusion: Three separate lots of the liquid hexavalent combined vaccine induced consistently protective antibody responses against all antigens. These results and the well established clinical tolerability of this combined vaccine make it suitable for primary immunization of infants at 2, 4, and 6 months of age.

Open Access Article

Follow-up of MMR Vaccination Status in Children Referred to a Pediatric Immunization Clinic on Account of Egg Allergy

Felicity Goodyear-Smith, Fleur Wong, Helen Petousis-Harris, Elizabeth Wilson and Nikki Turner
Pages 118 - 122
http://dx.doi.org/10.4161/hv.1.3.1888
Abstract | PDF

Aim: To determine timeliness and completeness of MMR immunisation uptake and general immunisation status of egg-allergic children referred to hospital for MMR vaccine who were referred back to their primary care providers with explanatory information that community-based vaccination is safe in these children.
Method: Referred children’s immunisation status obtained from referring practices. Where the practice had no record parents were contacted. Parents whose children had not received MMR were asked reasons for their choice. Timeliness of immunisations was examined for both MMR and the primary schedule. Practices referring more than one child to immunisation clinic were analysed to determine whether previous letters from the immunisation clinic influenced their referring practice.
Results: 82 children were eligible from 67 practices. MMR status was obtained for 78 (95% response rate). Of these 78, 73 (94%) received MMR vaccination with no reported adverse events: 8 (11%) on time, 54 (69%) late and 11 (14%) timeliness unknown. Five (6%) children had not received MMR vaccination. Three practices were unwilling to carry out MMR immunisation of egg-allergic children, even after recommendation from the immunisation clinic. Of the five parents whose children had not received MMR, two had actively decided against vaccination.
Discussion: 94% children received their MMR in primary care with no reported adverse effects. The current strategy utilised by the immunisation clinic appears to result in MMR immunisation of egg-allergic children. While the referral process may result in delayed immunisations, continued education of health professionals may improve timeliness and immunisation rates.

Open Access Article

Immunogenicity of the Hookworm Na-ASP-2 Vaccine Candidate: Characterization of Humoral and Cellular Responses after Vaccination in the Sprague Dawley Rat

Ricardo T. Fujiwara, Jeffrey Bethony, Lilian L. Bueno, Yan Wang, So Yeong Ahn, andre samuel, Maria Elena Bottazzi, Peter Hotez and Susana Mendez
Pages 123 - 128
http://dx.doi.org/10.4161/hv.1.3.1924
Abstract | PDF

The recombinant larval protein Na-ASP-2 from the human helminth parasite Necator americanus is a lead candidate for a human hookworm vaccine. We have characterized the humoral and cellular immune responses elicited by the Na-ASP-2 formulated with the aluminum-based adjuvant Alhydrogel® in the Sprague Dawley rat. We demonstrated that Na-ASP-2 vaccine induced a strong antibody response at all doses tested, as evidenced by high specific IgG1, IgG2a and IgM titers. High IgG antibody titers were maintained up to three months post vaccination and were boosted by an additional vaccine dose. Specific cell proliferation and a Th2 cytokine profile were also observed in peripheral blood of all rats immunized with the formulated vaccine. Host IL-6 levels were also significantly elevated. These data provide evidence that the immune response of the Na-ASP-2 vaccine is robust and durable and therefore suitable for the further clinical development of the Na-ASP-2 vaccine.