A booster dose of the measles vaccine
produces protective antibody responses and immunologic memory in children
receiving HIV therapy, US investigators report in the online edition of the Journal of Infectious Diseases. A viral load below 400 copies/ml was
associated with vaccine response.
“The present study reinforces the safety
and potential value of measles (re)vaccination, when administered with an
adequate CD4 cell % in the context of HAART [highly active antiretroviral
therapy], to achieve high response rates with persisting immunologic memory,”
write the investigators.
Measles can cause severe disease in
HIV-positive children. The infection is endemic in the world regions that have
the highest prevalence of HIV, and measles is therefore the cause of
significant levels of serious illness and death in HIV-positive children in
A measles vaccine has been
available since the 1960s. However, response rates to this live vaccine are reduced in
immune-suppressed people. There are also concerns about its safety when
administered to children with a low CD4 cell count.
Little is known about the immunity that a
booster dose of the vaccine provides to children taking antiretroviral therapy.
Investigators from the International
Maternal Adolescent AIDS Clinical Trials Group (IMPAACT) therefore designed a
study to assess the protective effect of measles revaccination. Their study
sample involved 193 children aged between 2 and 19 years. All were on stable
antiretroviral therapy and had a CD4 cell percentage above 15% and a viral load
below 30,000 copies. The children had previously received one or more dose of
the combined measles, mumps and rubella (MMR) vaccine. Measles antibody
concentrations were monitored before revaccination and then 8, 32 and 80
weeks after receiving the booster. A sub-set of 65 children was given another
dose of the MMR vaccine approximately four years later. Measles antibody levels
were measured before, and then 7 and 28 days later. The investigators
conducted a series of analyses to see which factors were associated with a
response to revaccination and the persistence of antibody memory.
On entry to the study, 83% of children had
detectable measles antibodies. In 52%, antibody levels were sufficient to
provide protection against the infection (plaque reduction neutralisation of or
above 120 miu/ml). Eight weeks after receiving the booster, the proportion of
patients with protective levels of antibodies had increased to 89%.
After controlling for potential
confounders, the investigators’ analysis showed that the only factor associated
with antibody response at this time was a viral load below 400 copies/ml (p
The vaccine appeared to be safe. Only 2% of
children experienced moderate to severe side-effects (three cases of fever; one
Revaccination provided long-term benefits.
When antibody levels were assessed 80 weeks after revaccination, the
investigators found that they were at protective levels in 80% of children.
The subgroup analysis indicated there were high levels of immunologic memory
following revaccination. The children in this analysis had a median CD4 cell
percentage of 35%. They received their second MMR booster dose a median of 4.24
years after initial revaccination. At this time, some 98% had detectable levels
of measles antibodies, and in 75% their level was sufficient to protect against
the infection. Seven days after revaccination, the proportion with protective
levels of antibodies had increased to 83% and this had increased again to 95% by day
28. A response to revaccination was associated with a viral load below 400
copies/ml (p = 0.03).
None of the children undergoing this second
revaccination experienced moderate or severe side-effects.
The author of an accompanying editorial
believes the study “provides promising information guiding measles vaccine use
among HIV-infected children”. However, she cautions that “A number of obstacles
still remain to reduction of global measles infection, especially among the
larger population of HIV-infected infants and children living in resource poor
settings.” These include sub-optimal prevention and diagnosis of HIV;
inadequate access to HIV therapy; and poor uptake of measles vaccination.
She concludes that the “study provides further
evidence to support recommendations for measles booster vaccination of
HIV-infected children on stable antiretroviral therapy with suppressed viral
loads”, adding “This observation can only be successful in preventing measles
morbidity and mortality if it is coupled globally with aggressive
identification and antiretroviral treatment of children with HIV infection.”