Vaccine xxx (2005) xxx–xxx
A novel synthetic adjuvant effectively enhances the immunogenicity
of the influenza vaccine
R. Segura-Vel´ azquez
a
, A. P´ erez-Torres
b
, G. Rosas
c
, A. Toledo
a
, M. Restelli
d
, E. Acosta
a
,
R. Corral
d
, F. Rosetti
b
, G. Fragoso
a
, S. Grinstein
d
, E. Sciutto
a,∗
a
Instituto de Investigaciones Biom´ edicas, A.P. 70228, Ciudad Universitaria, 04510 M´ exico, D.F., M´ exico
b
Facultad de Medicina, UNAM, M´ exico, D.F., M´ exico
c
Facultad de Medicina, UAEM, Cuernavaca, M´ exico
d
Laboratorio de Virolog´ ıa, Hospital del Ni ˜ no Ricardo Guti´ errez, Buenos Aires, Argentina
Received 9 June 2005; received in revised form 25 August 2005; accepted 5 September 2005
Abstract
Influenza vaccination is a key intervention to reduce morbidity and mortality provoked by this disease. To date, the challenge of improving
its efficacy remains unmet. The immunogenic synthetic peptide GK1 from Taenia crassiceps cysticerci was tested herein in its capacity
as adjuvant, co-administered with the inactivated anti-influenza vaccine before and after challenge with influenza virus in both young and
aged mice. Co-administration of GK1 with the influenza vaccine increased levels of anti-influenza antibodies in aged mice before and after
infection, reduced the local inflammation that accompanied influenza vaccination itself and favored virus clearance after infection in both
young and aged mice.
© 2005 Elsevier Ltd. All rights reserved.
Keywords: Influenza vaccine; Adjuvant; GK-1
1. Introduction
Senescence of the immune system is reflected at different
levels, e.g. defects in the expression of pattern-recognition
co-stimulatory molecules in antigen-presenting cells, dereg-
ulation of nitric oxide (NO) and cytokine production, and
altered balance of memory CD4+ T cells [1–3]. This decline
must be related to the impaired immunity conferred by infec-
tion or vaccination as age advances [4–6]. Global rise of
the aging population also causes an increase in the need
to improve immunity of the elderly, e.g. the UK govern-
ment’s actuary department has forecasted that 20% of the
population will be >65 years of age. This makes it of spe-
cial relevance to overcome the low vaccine efficacy against
different pathogens.
∗
Corresponding author. Tel.: +52 55 5622 3153; fax: +52 55 5622 3369.
E-mail address: edda@servidor.unam.mx (E. Sciutto).
Influenza is an acute febrile respiratory disease that rep-
resents a health problem responsible for thousands of yearly
hospitalization and deaths [7]. In this context, an improve-
ment in the response to influenza vaccination is one of the
clearest needs considering the low response of the elderly
compared to younger adults. Thus, enormous efforts are cur-
rently under way in order to improve the influenza vaccine [8].
Several novel strategies, including the use of immunomodu-
lators such as adjuvants, may overcome some of the defects of
aging immunity [9], since they are more effective in priming
the cellular and humoral responses. The oil-in-water adjuvant
emulsion MF59 may significantly improve vaccine immunity
[10,11]. MF59 is the most extensively explored and recently
approved adjuvant to be used in humans, albeit it does not
completely solve the low efficiency of the influenza vaccine
in the elderly, which still remains a challenge [12].
In this study, the immunostimulatory properties of a
parasite-derived synthetic peptide termed GK1 were exper-
imentally explored when administered together with the
0264-410X/$ – see front matter © 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.vaccine.2005.09.014
JVAC-5664; No. of Pages 8