Intradermal influenza vaccine and new devices: a promising chance for vaccine improvement

Introduction: The main public health strategy for reducing the influenza burden is annual vaccination. However, because the immune response in the elderly and frail subjects is known to be less vigorous than in younger adults, novel strategies have been explored in the last decade to augment immune response after immunization. These have included an increased dosage, multiple dose vaccinations, use of vaccine adjuvants and more efficient routes of vaccine delivery. Areas covered: This review discusses recent advances in intradermally administered influenza vaccines with particular attention to immunogenicity and safety data from clinical trials performed using appropriate injection systems which, combining consistent injection depth and volume, safety, simplicity and ease-of-use, allowed large scale evaluation. Expert opinion: Substantial experience has been accumulated with Intanza 9 and Intanza 15 μg/IDflu 15 μg, administered using BD's Soluvia™ device, and are the first intradermal trivalent inactivated split-virion influenza vaccines to be licensed for use in 18 – 59 year adults and in elderly people, respectively. Clinical data showed that they are safe and immunogenic and can offer significant advantages in terms of higher acceptability, higher immunogenicity in the elderly and dose-sparing in adults younger than 60 years when compared with intramuscularly administered vaccine.

[1]  M. Prausnitz,et al.  Enhanced memory responses to seasonal H1N1 influenza vaccination of the skin with the use of vaccine-coated microneedles. , 2010, The Journal of infectious diseases.

[2]  T. H. Weller,et al.  Immunologic Reactions Following the Intradermal Inoculation of Influenza A and B Vaccine.∗ , 1948, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[3]  Médecine Santé-Voyage An Advisory Committee Statement (ACS) , 2009 .

[4]  G. Schuler,et al.  Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization. , 1993, The Journal of clinical investigation.

[5]  J. Stockman,et al.  Dissolving polymer microneedle patches for influenza vaccination , 2012 .

[6]  L. Sticchi,et al.  Antibody response against heterogeneous circulating influenza virus strains elicited by MF59- and non-adjuvanted vaccines during seasons with good or partial matching between vaccine strain and clinical isolates. , 2010, Vaccine.

[7]  G. Leroux-Roels,et al.  Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial , 2007, The Lancet.

[8]  R. Couch,et al.  The immunizing effect of influenza A/New Jersey/76 (Hsw1N1) virus vaccine administered intradermally and intramuscularly to adults. , 1977, The Journal of infectious diseases.

[9]  P. van Damme,et al.  Intradermal influenza vaccine for older adults: a randomized controlled multicenter phase III study. , 2009, Vaccine.

[10]  R. Harpaz,et al.  Prevention of plague: recommendations of the Advisory Committee on Immunization Practices (ACIP). , 1996, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[11]  C. A. Phillips,et al.  Purified influenza vaccine: clinical and serologic responses to varying doses and different routes of immunization. , 1970, The Journal of infectious diseases.

[12]  M. Goldfield,et al.  A comparison of the intradermal and subcutaneous routes of influenza vaccination with A/New Jersey/76 (swine flu) and A/Victoria/75: report of a study and review of the literature. , 1979, American journal of public health.

[13]  F. Newman,et al.  Serum antibody responses after intradermal vaccination against influenza. , 2004, The New England journal of medicine.

[14]  P. Thongcharoen,et al.  Antibody responses after dose-sparing intradermal influenza vaccination. , 2007, Vaccine.

[15]  M. Marks,et al.  Intradermal influenza immunization. Experience with Hong Kong vaccine. , 1971, The American review of respiratory disease.

[16]  A. Nicoll,et al.  Risk groups and other target groups - preliminary ECDC guidance for developing influenza vaccination recommendations for the season 2010-11. , 2010, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[17]  E. Morelon,et al.  Immunogenicity and safety of intradermal influenza vaccination in renal transplant patients who were non-responders to conventional influenza vaccination. , 2010, Vaccine.

[18]  Laura Kann,et al.  Youth risk behavior surveillance--United States, 2003. , 2004, Morbidity and mortality weekly report. Surveillance summaries.

[19]  P. Perine,et al.  Low-dose intradermal and intramuscular vaccination against hepatitis B. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  Stephanie L. Dickinson,et al.  Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials. , 2009, Vaccine.

[21]  Ruben Fl,et al.  Intradermal administration of bivalent and monovalent influenza vaccines. , 1977 .

[22]  G. Leroux-Roels,et al.  Seasonal influenza vaccine delivered by intradermal microinjection: A randomised controlled safety and immunogenicity trial in adults. , 2008, Vaccine.

[23]  C. Thompson,et al.  Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets. , 1993, Journal of immunology.

[24]  Shinn-Jang Hwang,et al.  Immunogenicity and tolerability of an AS03(A)-adjuvanted prepandemic influenza vaccine: a phase III study in a large population of Asian adults. , 2009, Vaccine.

[25]  G. Glenn,et al.  Dose sparing with intradermal injection of influenza vaccine. , 2004, The New England journal of medicine.

[26]  Marks Mi,et al.  Intradermal influenza immunization. Experience with Hong Kong vaccine. , 1971 .

[27]  A. Floreani,et al.  Comparison of three different influenza vaccines in institutionalised elderly. , 2001, Vaccine.

[28]  H. Furrer,et al.  Randomized, double-blind comparative trial of subunit and virosomal influenza vaccines for immunocompromised patients. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[29]  A. Osterhaus,et al.  Mismatch between the 1997/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine‐induced antibody response to this strain in the elderly , 2000, Journal of medical virology.

[30]  M. Zambon,et al.  Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza , 2001, The Lancet.

[31]  R. Larke,et al.  Comparison of responses to influenza A/New Jersey/76-A/Victoria/75 virus vaccine administered intradermally or subcutaneously to adults with chronic respiratory disease. , 1979, The Journal of infectious diseases.

[32]  W. P. Glezen,et al.  Trivalent Live Attenuated Intranasal Influenza Vaccine Administered During the 2003–2004 Influenza Type A (H3N2) Outbreak Provided Immediate, Direct, and Indirect Protection in Children , 2007, Pediatrics.

[33]  D. Novicki,et al.  Safety of MF59 adjuvant. , 2008, Vaccine.

[34]  P. van Damme,et al.  Clinical studies assessing immunogenicity and safety of intradermally administered influenza vaccines , 2010, Expert opinion on drug delivery.

[35]  Kwok-Hung Chan,et al.  Immunogenicity and safety of intradermal versus intramuscular route of influenza immunization in infants less than 6 months of age: a randomized controlled trial. , 2009, Vaccine.

[36]  B. Guy,et al.  Intradermal, epidermal and transcutaneous vaccination: from immunology to clinical practice , 2008, Expert review of vaccines.

[37]  B. Spellberg The cutaneous citadel: a holistic view of skin and immunity. , 2000, Life sciences.

[38]  F. de Looze,et al.  Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial. , 2008, The Journal of infectious diseases.

[39]  S. Oh,et al.  Dose sparing strategy with intradermal influenza vaccination in patients with solid cancer , 2009, Journal of Medical Virology.

[40]  Kyoung-Mi Park,et al.  Improved protection against avian influenza H5N1 virus by a single vaccination with virus-like particles in skin using microneedles. , 2010, Antiviral research.

[41]  N. Cox,et al.  Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. , 2009 .

[42]  C. Bridges,et al.  The annual impact of seasonal influenza in the US: measuring disease burden and costs. , 2007, Vaccine.

[43]  M. Prausnitz,et al.  Improved influenza vaccination in the skin using vaccine coated microneedles. , 2009, Vaccine.

[44]  C. Caux,et al.  Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria1 , 2006, The Journal of Immunology.

[45]  N. Mickuvienė,et al.  Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial , 2009, BMC medicine.

[46]  W. Dupont,et al.  A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. , 1994, The Journal of infectious diseases.

[47]  P. Lambert,et al.  Intradermal vaccine delivery: will new delivery systems transform vaccine administration? , 2008, Vaccine.

[48]  A. Monto,et al.  Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. , 2006, The New England journal of medicine.

[49]  F. Newman,et al.  Comparative immunogenicity of trivalent influenza vaccine administered by intradermal or intramuscular route in healthy adults. , 2007, Vaccine.

[50]  M. Thobaben,et al.  Prevention and Control of Influenza , 2003, MMWR. Morbidity and mortality weekly report.

[51]  A. Banzhoff,et al.  Antibody response of patients after postexposure rabies vaccination with small intradermal doses of purified chick embryo cell vaccine or purified Vero cell rabies vaccine. , 2000, Bulletin of the World Health Organization.

[52]  Roxanne Nelson Influenza vaccine shortage hits the USA , 2003, The Lancet.

[53]  J. Szwed,et al.  Response to intradermal vaccination with A2, Hong Kong variant, influenza vaccine. , 1969, The New England journal of medicine.

[54]  K. Nichol,et al.  The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. , 2003, Vaccine.

[55]  A. Podda The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. , 2001, Vaccine.

[56]  Kwok-Hung Chan,et al.  Immunogenicity and Safety of Intradermal Influenza Immunization at a Reduced Dose in Healthy Children , 2007, Pediatrics.

[57]  R. Rappuoli,et al.  An MF59-adjuvanted inactivated influenza vaccine containing A/Panama/1999 (H3N2) induced broader serological protection against heterovariant influenza virus strain A/Fujian/2002 than a subunit and a split influenza vaccine. , 2006, Vaccine.

[58]  M. Klein,et al.  The response of infants and children to Asian influenza vaccine administered by intradermal and subcutaneous routes. , 1961, The Journal of pediatrics.

[59]  G. Rimmelzwaan,et al.  Intradermal influenza vaccination in immunocompromized patients is immunogenic and feasible. , 2009, Vaccine.

[60]  A. Falsey,et al.  Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. , 2009, The Journal of infectious diseases.

[61]  P. van Damme,et al.  Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. , 2009, Vaccine.

[62]  Szwed Jj,et al.  Response to intradermal vaccination with A2, Hong Kong variant, influenza vaccine. , 1969 .

[63]  R B Couch,et al.  Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period. , 1997, Vaccine.

[64]  R. Couch,et al.  Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects. , 2007, Vaccine.

[65]  R. Couch,et al.  Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons. , 2006, Archives of internal medicine.

[66]  C. Herzog,et al.  Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration. , 2009, Vaccine.

[67]  F. Ruben,et al.  Intradermal administration of bivalent and monovalent influenza vaccines. , 1977, Annals of allergy.

[68]  F. Pregliasco,et al.  Immunogenicity and safety of three commercial influenza vaccines in institutionalized elderly , 2001, Aging.

[69]  L. Sticchi,et al.  Cross-protection by MF59-adjuvanted influenza vaccine: neutralizing and haemagglutination-inhibiting antibody activity against A(H3N2) drifted influenza viruses. , 2008, Vaccine.

[70]  B. Chuaychoo,et al.  The immunogenicity of intradermal influenza vaccination in COPD patients. , 2010, Vaccine.

[71]  J. Mccarroll,et al.  Immunization with Asian-strain influenza vaccine: equivalence of the subcutaneous and intradermal routes. , 1958, New England Journal of Medicine.

[72]  M. Cooney,et al.  Efficacy of intradermally administered A2 Hong Kong vaccine. , 1970, JAMA.

[73]  A. Ambrozaitis,et al.  Immunogenicity, large scale safety and lot consistency of an intradermal influenza vaccine in adults aged 18–60 years: Randomized, controlled, Phase III trial , 2010, Human vaccines.

[74]  Y. Maeno,et al.  Improved antibody responses in infants less than 1 year old using intradermal influenza vaccination. , 2008, Vaccine.

[75]  P. van Damme,et al.  Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study , 2010, BMC infectious diseases.

[76]  J. Nauta,et al.  The virosomal influenza vaccine Invivac: immunogenicity and tolerability compared to an adjuvanted influenza vaccine (Fluad in elderly subjects. , 2006, Vaccine.

[77]  O. Manuel,et al.  Immunogenicity and Safety of an Intradermal Boosting Strategy for Vaccination Against Influenza in Lung Transplant Recipients , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[78]  T. Kase,et al.  Cross-reactivity of influenza A (H3N2) hemagglutination-inhibition antibodies induced by an inactivated influenza vaccine. , 2006, Vaccine.

[79]  K. Edwards,et al.  Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. , 2002, The Journal of infectious diseases.

[80]  W. P. Boger,et al.  [Subcutaneous and intradermal vaccination with Asian influenza vaccine]. , 1957, Journal of the American Medical Association.

[81]  N. Cox,et al.  Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). , 2006, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[82]  W. Bancroft,et al.  Clinical evaluation of low-dose intradermally administered hepatitis B virus vaccine. A cost reduction strategy. , 1985, JAMA.

[83]  Cécile Viboud,et al.  Antibody response to influenza vaccination in the elderly: a quantitative review. , 2006, Vaccine.

[84]  J. Devaster,et al.  Immunogenicity and safety in adults of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03A-adjuvant: preliminary report of an observer-blind, randomised trial. , 2010, Vaccine.