Responses to A(H1N1)pdm09 influenza vaccines in participants previously vaccinated with seasonal influenza vaccine: a randomized, observer-blind, controlled study

Sumita Roy-Ghanta, Robbert Van der Most, Ping Li, David W Vaughn, Sumita Roy-Ghanta, Robbert Van der Most, Ping Li, David W Vaughn

Abstract

Background: Prior receipt of a trivalent seasonal influenza vaccine (TIV) can affect hemagglutination inhibition (HI) antibody responses to pandemic influenza vaccines. We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety.

Methods: Healthy adults (aged 19-40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and postvaccination responses of HI and neutralizing antibody, CD4(+)/CD8(+) T cells, memory B cells, and plasmablasts were assessed.

Results: Ninety-nine of the 133 participants enrolled completed the study. No vaccine-related serious adverse events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody and CD4(+) T-cell and memory B-cell responses to the pandemic vaccine tended to be diminished. Vaccine adjuvantation led to increased responses of vaccine-homologous and -heterologous HI and neutralizing antibodies and CD4(+) T cells, homologous memory B cells, and plasmablasts.

Conclusions: In healthy adults, prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09 vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune interference between the influenza vaccines. No safety concerns were observed.

Registration: Clinical Trials.gov identifier NCT00707967.

Keywords: A(H1N1)pdm09 vaccine; AS03; B cells; CD4+ T cells; HI antibody; TIV; immune interference; neutralizing antibody; pandemic influenza; plasmablasts.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
CONSORT diagram of study flow. A/Cal*, A(H1N1)pdm09 vaccine. Group A received trivalent seasonal influenza vaccine (TIV) and 2 doses of A(H1N1)pdm09 (3.75 µg) /AS03. Group B received TIV and 2 doses of A(H1N1)pdm09 (15 µg). Group C received saline and 2 doses of A(H1N1)pdm09 (3.75 µg) /AS03. Group D received saline and 2 doses of A(H1N1)pdm09 (15 µg). Abbreviations: D, day; N, number of participants who received the vaccine and for whom data were available.
Figure 2.
Figure 2.
A(H1N1)pdm09-specific and A/Brisbane/59/2007-specific hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses. A(H1N1)pdm09-specific (panel A) and A/Brisbane/59/2007-specific (panel B) HI and NAb responses shown are of the according-to-protocol cohort for immunogenicity (ATP-I cohort) at D164, except those for day 304 (from ATP-I cohort at day 304). Group A received trivalent seasonal influenza vaccine (TIV) at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group B received TIV at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143. Group C received saline at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group D received saline at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143. Abbreviations: CI, confidence interval; GMT, geometric mean titer.
Figure 3.
Figure 3.
A(H1N1)pdm09-specific memory B-cell responses to A(H1N1)pdm vaccine and proportion of plasmablasts (CD27+/CD38+) among B cells (CD19+/CD3−) after trivalent seasonal influenza vaccine (TIV) vaccination. A, Data shown are of the according-to-protocol cohort for immunogenicity at day 304. Group A received TIV at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group B received TIV at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143. Group C received saline at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group D received saline at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143. Data are reported as the percentages of A/California/7/2009-specific memory B cells of all B cells, with first and third quartiles, and the minimum/maximum values measured. B, Geometric means of plasmablast (CD27+/CD38+) frequencies expressed as a percentage of B cells (CD20lo/CD19+/CD3−) after administration of TIV (days 0–129). Abbreviation: D, day.
Figure 4.
Figure 4.
Frequency of A(H1N1)pdm09-specific and A/Brisbane/59/2007-specific CD4+ T cells expressing at least 2 immune markers. Data shown are of the according-to-protocol cohort for immunogenicity at day 304. Group A received trivalent seasonal influenza vaccine (TIV) at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group B received TIV at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143. Group C received saline at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group D received saline at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143. Data are reported as the percentages of A(H1N1)pdm09-specific (A) or A/Brisbane/59/2007-specific (B) CD4+ T cells expressing (after in vitro stimulation) at least 2 immune markers among interferon-gamma, interleukin-2, tumor necrosis factor-alpha, and CD40L of all CD4+ T cells, with first and third quartiles, and the minimum/maximum values measured. Abbreviation: D, day.
Figure 5.
Figure 5.
Incidence of solicited symptoms after the administration of trivalent seasonal influenza vaccine (TIV) or placebo and after each of the 2 doses of A(H1N1)pdm09 vaccine. Mean percentage of participants with 95% confidence interval (CI) experiencing solicited local (A) and general (B) adverse events (AEs) reported within 7 days postvaccination are shown for all participants for whom at least 1 administration of vaccine or placebo was documented (the total vaccinated cohort). Group A received TIV at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group B received TIV at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143. Group C received saline at day 0 and A(H1N1)pdm09 (3.75 µg)/AS03 at day 122 and day 143. Group D received saline at day 0 and A(H1N1)pdm09 (15 µg) at day 122 and day 143.

References

    1. Jayaraman A, Pappas C, Raman R, et al. A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets. PLoS ONE. 2011;6:e17616.
    1. World Health Organization. Pandemic H1N1 (2009)—update 112. Global Alert and Response Weekly Update. 2010. . Accessed 23 May 2013.
    1. Dawood FS, Iuliano AD, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis. 2012;12:687–95.
    1. Greenberg ME, Lai MH, Hartel GF, et al. Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med. 2009;361:2405–13.
    1. Plennevaux E, Sheldon E, Blatter M, Reeves-Hoché M-K, Denis M. Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials. Lancet. 2010;375:41–8.
    1. Clark TW, Pareek M, Hoschler K, et al. Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine. N Engl J Med. 2009;361:2424–35.
    1. Jennings LC, Monto AS, Chan PK, Szucs TD, Nicholson KG. Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans. Lancet Infect Dis. 2008;8:650–8.
    1. Roman F, Vaman T, Kafeja F, Hanon E, Van Damme P. AS03A-adjuvanted influenza A (H1N1) 2009 vaccine for adults up to 85 years of age. Clin Infect Dis. 2010;51:668–77.
    1. Roman F, Clément F, Dewé W, et al. Effect on cellular and humoral immune responses of the AS03 Adjuvant System in an A/H1N1/2009 influenza virus vaccine administered to adults during two randomized controlled trials. Clin Vaccine Immunol. 2011;18:835–43.
    1. Andrews NJ, Walker WT, Finn A, et al. Predictors of immune response and reactogenicity to AS03B-adjuvanted split virion and non-adjuvanted whole virion H1N1 (2009) pandemic influenza vaccines. Vaccine. 2011;29:7913–9.
    1. Roman F, Vaman T, Gerlach B, Markendorf A, Gillard P, Devaster J-M. 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. Vaccine. 2010;28:1740–5.
    1. Peeters M, Regner S, Vaman T, Devaster J-M, Rombo L. Safety and immunogenicity of an AS03-adjuvanted A(H1N1)pmd09 vaccine administered simultaneously or sequentially with a seasonal trivalent vaccine in adults 61 years or older: data from two multicentre randomised trials. Vaccine. 2012;30:6483–91.
    1. Huijskens E, Rossen J, Mulder P, et al. Immunogenicity, boostability, and sustainability of the immune response after vaccination against influenza A virus (H1N1) 2009 in a healthy population. Clin Vaccine Immunol. 2011;18:1401–5.
    1. Van Damme P, Kafeja F, Bambure V, et al. Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized study in adults aged 18–60 years and older. Hum Vaccin Immunother. 2013;9:1512–22.
    1. Uno S, Kimachi K, Kei J, et al. Effect of prior vaccination with a seasonal trivalent influenza vaccine on the antibody response to the influenza pandemic H1N1 2009 vaccine: a randomized controlled trial. Microbiol Immunol. 2011;55:783–9.
    1. Wu J, Zhong X, Li CK, et al. Optimal vaccination strategies for 2009 pandemic H1N1 and seasonal influenza vaccines in humans. Vaccine. 2011;29:1009–16.
    1. Zhou Y, Ng DM, Seto WH, et al. Seroprevalence of pandemic H1N1 antibody among health care workers in Hong Kong following receipt of monovalent 2009 H1N1 influenza vaccine. PLoS One. 2011;6:e27169.
    1. Choi YS, Baek YH, Kang W, et al. Reduced antibody responses to the pandemic (H1N1) 2009 vaccine after recent seasonal influenza vaccination. Clin Vaccine Immunol. 2011;18:1519–23.
    1. Nolan T, McVernon J, Skeljo M, et al. Immunogenicity of a monovalent 2009 influenza A(H1N1) vaccine in infants and children: a randomized trial. JAMA. 2010;303:37–46.
    1. Nolan T, Richmond PC, Formica NT, et al. Safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in infants and children. Vaccine. 2008;26:6383–91.
    1. Leroux-Roels I, Roman F, Forgus S, et al. Priming with AS03A-adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: an open non-randomised extension of a double-blind randomised primary study. Vaccine. 2010;28:849–57.
    1. Kim JH, Skountzou I, Compans R, Jacob J. Original antigenic sin responses to influenza viruses. J Immunol. 2009;183:3294–301.
    1. Fazekas de St Groth S, Webster RG. Disquisitions on original Antigenic Sin. I. Evidence in man. J Exp Med. 1966;124:331–45.
    1. Wrammert J, Smith K, Miller J, et al. Rapid cloning of high affinity human monoclonal antibodies against influenza virus. Nature. 2008;453:667–71.
    1. Gulati U, Kumari K, Wu W, Keitel WA, Air GM. Amount and avidity of serum antibodies against native glycoproteins and denatured virus after repeated influenza whole-virus vaccination. Vaccine. 2005;23:1414–25.
    1. Kim JH, Davis WG, Sambhara S, Jacob J. Strategies to alleviate original antigenic sin responses to influenza viruses. Proc Natl Acad Sci U S A. 2012;109:13751–6.
    1. Moris P, van der Most R, Leroux-Roels I, et al. H5N1 influenza vaccine formulated with AS03A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin Immunol. 2011;31:443–54.
    1. Khurana S, Chearwae W, Castellino F, et al. Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Sci Transl Med. 2010;2 15ra5.
    1. Khurana S, Verma N, Yewdell JW, et al. MF59 adjuvant enhances diversity and affinity of antibody-mediated immune response to pandemic influenza vaccines. Sci Transl Med. 2011;3 85ra48.
    1. Morel S, Didierlaurent A, Bourguignon P, et al. Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine. 2011;29:2461–73.
    1. Hehme NW, Künzel W, Petschke F, et al. Ten years of experience with the trivalent split-influenza vaccine, Fluarix™. Clin Drug Invest. 2002;22:751–69.
    1. European Agency for Proprietary Medicinal Products. European Agency for the Evaluation of Medicinal Products (CHMP); 2007. Guideline on influenza vaccine prepared from viruses with the potential to cause a pandemic and intended for use outside of the core dossier context (EMEA/CHMP/VWP/263499/2006)
    1. US Food and Drug Administration. Guidance for Industry: Clinical Data Needed to Support the Licensure of Pandemic Influenza Vaccines. 2007.
    1. Deenick EK, Ma CS. The regulation and role of T follicular helper cells in immunity. Immunology. 2011;134:361–7.
    1. Treanor JJ, Campbell JD, Brady RC, et al. Rapid licensure of a new, inactivated influenza vaccine in the United States. Hum Vaccin. 2005;1:239–44.
    1. Barker CI, Snape MD. Pandemic influenza A H1N1 vaccines and narcolepsy: vaccine safety surveillance in action. Lancet Infect Dis. 2014;14:227–38.
    1. De la Herrán-Arita AK, Kornum BR, Mahlios J, et al. CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy. Sci Transl Med. 2013;5 216ra176.

Source: PubMed

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