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New Adjuvant Permits Early Pneumococcal Immunization in Newborn Monkeys

Compound May Help Protect Human Infants Earlier with Fewer Doses

March 23, 2017

The Centers for Disease Control and Prevention (CDC) recommends that children receive pneumococcal conjugate vaccinations (PCV13) against potentially life-threatening pneumococcal disease at two, four and six months of age. Earlier immunization would confer greater protection when infants are most vulnerable to disease, but newborns’ immature immune systems limit their capacity to respond effectively to PCV13 and establish immunity.

Now, researchers have discovered that newborn monkeys given a single dose of PCV13 along with an experimental adjuvant (a substance that enhances an immune response) on the first day of life rapidly developed a strong immunological response against pneumococcal bacteria, giving hope that the same may be true for human newborns. The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, supported the study. The results appear online Thursday in JCI Insight.

The study, led by David Dowling, Ph.D., and Ofer Levy, M.D., Ph.D., of Boston Children’s Hospital, showed that the experimental adjuvant 3M-052 added to PCV13 prompted newborn human immune cells to respond to the vaccine in a similar way to adult human immune cells. Researchers also found the adjuvant’s formulation in insoluble fat prevented the compound from moving beyond the injection site when tested in rodents, minimizing the potential for adverse effects.

Researchers then gave four groups of five newborn monkeys a single injection of either saline, 3M-052 only, the current PCV13 formulation, or PCV13 plus 3M-052. Scientists then evaluated the monkeys for antibodies to pneumococcal bacteria and other signals of protection one and two months after immunization. The first three injection groups showed modest or no detectable responses. The group that received PCV13 plus 3M-052 had antibody responses 10-100 times stronger at one month than those that received PCV13 alone, and with no serious adverse events. This result indicates that a currently available pneumococcal vaccine modified with the 3M-052 adjuvant enables newborn monkeys to mount a robust immune response predictive of protection.

Further research is needed to ensure that PCV13 with 3M-052 is safe and appropriate for human trials. The researchers’ goal is to develop an effective pneumococcal vaccine delivered in early life to protect newborns against deadly infection. The Journal of Allergy and Clinical Immunology released a related study today in which the same research team found that a similar adjuvant was also safe and effective when combined with an experimental tuberculosis vaccine and tested in newborn rodents.

ARTICLES:
D Dowling et al. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth. JCI Insight DOI: 10.1172/jci.insight.91020 (2017).

D Dowling et al. Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses. Journal of Allergy and Clinical Immunology DOI: 10.1016/j.jaci.2016.12.985 (2017).

WHO:
Mercy PrabhuDas, Ph.D., M.B.A., of NIAID’s Division of Allergy, Immunology and Transplantation, and Wolfgang Leitner, M.S.C., Ph.D., Chief of the Innate Immunity Section in DAIT, are both available for comment.