HIV-positive patients with a CD4 cell count
below 350 cells/mm3 have an impaired immune response to the seasonal
influenza (flu) vaccine, Swiss investigators report in the September 10th
edition of AIDS. They recommend that all HIV-positive patients
should have an annual influenza vaccine to help them to establish flu-specific
memory immune cells, the formation of which can be difficult after the immune
system suffers serious damage.
The study was undertaken because investigators
from Basel wished to assess responses to the seasonal influenza vaccine in
HIV-positive patients. Blood samples were therefore taken from 24 HIV-positive
patients and 31 HIV-negative controls immediately before administration of the
seasonal flu vaccine in 2007-2008 and again approximately 30 days later. The
production of two forms of influenza antibodies – IgM and IgG – and levels of
flu-specific CD4 cells were measured.
All the HIV-positive patients had been
taking antiretroviral therapy for at least three months and had a viral load
below 200 copies/ml.
In HIV-negative individuals, median levels
of influenza-specific IgM and IgG increased significantly after the receipt of the
vaccine. In addition, increases in influenza-specific CD4 cell counts were observed
in 92% of individuals.
Amongst HIV-positive patients with
well-preserved immunity (a CD4 cell count above 350 cells/mm3), the
administration of the vaccine lead to significant increases in levels of
flu-specific IgM and IgG. However, only 64% of patients had an increase in
their flu-specific CD4 cell count.
A poor response to the vaccine was seen in
the HIV-positive patients whose CD4 cell count was below 350 cells/mm3.
No significant increase in influenza-specific IgM antibody levels were seen, and only
two patients had any IgM response at all. Moreover, only 44% of patients had an
increase in their influenza-specific CD4 cell count. However, a significant increase
in levels of post-vaccination influenza-specific IgG was observed.
“Increasing levels of IgG in this study
group most likely reflects a memory response”, comment the investigators. They
believe that this finding is important and “provides an immunologic rationale
supporting the recommendation of annual influenza vaccinations throughout the
course of HIV infection.”
Such vaccinations when a patient’s immune
system is intact build up “broad and long-lasting” B-cell memory.
The importance of such memory cells was
shown in the recent H1N1 pandemic. Children were especially vulnerable to this
strain of flu because they lacked the protective antibodies that are developed
from contact with earlier strains of flu.
“These preliminary data should trigger
future research aiming to understand the molecular basis of the observed lack
of IgM-production”, recommend the investigators.
The findings of the study also have significance
for clinical practice as they “lend support to strictly enacting annual
influenza-vaccination in all HIV-infected individuals regardless of their CD4+
These findings, which broadly correspond with findings from a sample of US patients showing that lack of response to H1N1 vaccine was associated with a low CD4 count, suggest that people with HIV with higher CD4 counts may derive the greatest benefit from current influenza vaccines, and that more research is needed to determine how to improve influenza vaccine responses in people with low CD4 counts.
In parrticular, argue the authors of a recent editorial comment in the journal AIDS, ensuring annual influenza vaccination in people with higher CD4 counts is likely to promote the build-up of B-cell memory while immunological competence is still maintained, ensuring that any subsequent CD4 cell decline does not impair responses to future influenza vaccinations.