A SINGLE injection at birth may be all it will take to protect newborn babies from a variety of dangerous infections. Babies are particularly vulnerable during their first few weeks of life because their immature immune system cannot generate a strong response to invading bacteria and viruses. Now it seems that a gentle nudge to their immune system may be enough to make it fight off disease.
Most vaccines do not produce lasting immunity in newborn babies. Instead, infants have to wait for vaccination until several months after birth and need several doses in order to encourage their sluggish immune memory. This can cause problems, especially in poorer countries where access to medical care may be inadequate. 鈥淚n many cases, the only time a child will meet a healthcare provider is the day they are born,鈥� says Ofer Levy, an infectious disease specialist at Children鈥檚 Hospital Boston. 鈥淭here is this major need to improve the vaccination of newborns.鈥�
鈥淚nfants can鈥檛 be vaccinated until they are months old, and need several doses to prompt their sluggish immune memory鈥�
Advertisement
According to the lastest thinking, newborns are capable of mounting adult-like inflammatory responses, but their ability to do so is 鈥渕uted鈥� by their immune systems. This muting could be necessary in the womb to prevent the immune systems of mother and fetus from clashing, leading to miscarriage or premature birth. In newborns, however, it might be possible to 鈥渦nmute鈥� the immune system to make vaccination more effective or provide a more vigorous defence against pathogens.
Levy and his colleagues think they may have found a way of doing just that. The team has been studying a group of molecules called Toll-like receptors (TLRs), which are found on the surface of certain white blood cells. They act as sentinels against invading bacteria or viruses, detecting foreign particles and triggering the rest of the body鈥檚 immune response. Molecules that stimulate TLRs are already being added to vaccines in clinical trials with older children and adults to try to stimulate their immune systems and thereby increase the effectiveness of the vaccines.
In newborn babies, however, most TLR-stimulating molecules trigger only one-hundredth to one-thousandth the response that they do in adults. There is one exception: Levy鈥檚 team has found that molecules that stimulate a receptor called TLR8 provoke a much stronger immune reaction. White blood cells taken from newborns responded as vigorously as adult cells to the TLR8 activators, producing adult-like quantities of the signalling molecules IL-12 and TNF-alpha, which stimulate the immune system (Blood, DOI: 10.1182/blood-2005-12-4821). 鈥淲e have found a stimulus that is able to fully activate immune responses in a newborn baby,鈥� says Levy. 鈥淪ome would consider this to be the holy grail of immunisation in the newborn.鈥�
鈥淭hese substances made white blood cells from infants produce adult-like quantities of signalling molecules鈥�
The discovery might open the door to developing many more vaccines that work in newborns. By adding TLR8 activators to vaccine formulations, vaccine developers may be able to boost newborns鈥� immune systems to the point that vaccines can be given in a single dose at birth, rather than in multiple doses several months later. Though the researchers hope to begin testing this possibility in animals, any human vaccines using this principle will be many years in the future.
Levy and others also caution that there may be unforeseen dangers in boosting the immune systems of infants, since there may be good reasons for keeping it turned down. 鈥淭he baby is in this sterile sac in utero then suddenly, Bam! You鈥檙e exposed to everything,鈥� says Levy. 鈥淚magine if you had a very pro-inflammatory immune system. The baby would be in total shock.鈥�
Levy hopes that a TLR8 activator, perhaps coupled to the viral proteins in a vaccine, would deliver a boost that is focused tightly enough not to cause problems, but whether this is possible remains unproven. 鈥淚s there any potential for harm from turning on that one switch?鈥� asks Paul McCray, an expert in newborn immune systems at the University of Iowa. 鈥淭he answer to that is unknown.鈥�
