People with HIV with higher CD4 counts should not miss seasonal flu jabs

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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.

Glossary

strain

A variant characterised by a specific genotype.

 

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

memory cell

A long-lived lymphocyte that carries the antibody or receptor for a specific antigen (after a first exposure to this antigen) and remains in a less than mature state until a second exposure to the antigen, at which time it mounts a more effective immune response than a cell which has not been exposed previously. 

CD4 cells

The primary white blood cells of the immune system, which signal to other immune system cells how and when to fight infections. HIV preferentially infects and destroys CD4 cells, which are also known as CD4+ T cells or T helper cells.

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+ T-cell count.”

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.

References

Fritz S et al. Virosomal influenza-vaccine induced immunity in HIV-infected individuals with high versus low CD4+ T-cell counts: clues towards a rational vaccination strategy. AIDS 24: 2287-90, 2010.