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The Wide World of Vaccines

December 2018

Neonatal Pertussis Vaccine–Another Strategy to Prevent Pertussis in Young Infants?

 

Christopher J. Harrison, MD, FAAP, FPIDS | Director, Infectious Diseases Research Laboratory | Director, Vaccine and Treatment Evaluation Unit | Professor of Pediatrics, UMKC School of Medicine

Pertussis in the first six months of life has the highest morbidity and mortality.1 Vaccine-induced protection against pertussis from current infant vaccine schedules is absent in the first months and is not fully developed until after 7 months of age, although there is some protection even with one dose.2 Repeated attempts at protecting these younger infants have included neonatal immunization, cocooning and maternal third trimester TdaP. Neonatal immunization with TdaP has produced mixed results in studies so far. There have been concerns that maternal antibody blunts pertussis vaccine response in newborns and that pertussis vaccine may alter subsequent responses to vaccines already in the current infant schedule. Some also theorize that poor vaccine response3 may be due to the D and T components. So, another strategy could be monovalent acellular pertussis vaccine (maP) at birth.

Recently, an Australian group randomized 440 term healthy newborns to receive at birth maP vaccine plus hepatitis B vaccine (HBV) or HBV alone (417 completed the study; N=212 with maP+ HBV and N=205 HBV only).4 The investigational aP vaccine contained pertussis toxin (PT) 25µg, pertactin (PRN) 8 µg, filamentous haemagglutinin (FHA) 25 µg and 0.5 mg aluminum hydroxide from GlaxoSmithKline. The authors evaluated safety plus antibody responses to both pertussis antigens and to standard infant vaccines (using the Australian schedule, which is a bit different than the U.S. schedule). Titers were assayed at 6, 10, 24, and 32 weeks of age. Infants were stratified for analysis based on maternal receipt of any aP-containing vaccine or maternal pertussis disease within the past five years.

Local and systemic adverse events were similar between both groups at all time points.

Quick and sustained robust response to neonatal maP dose. At 10 weeks of age, antibody to both PT and PRN were detected more often in the maP+HBV group than in the HBV-only group, 192/206 (93.2%) versus 98/193 (50.8%) respectively, P < .001. Further, geometric mean concentrations (GMC) for PT IgG were four times higher in the maP group at 10 weeks and also higher at each time point tested, P <0.001 for all but 32 weeks, which was P=0.01. Figure 1, Panel 1.

Figure 1. Panel 1. Antibody to PT in infants receiving monovalent acellular pertussis vaccine (maP) plus hepatitis B vaccine (HBV) compared to infants receiving only HBV at birth.

Panel 2. Responses to standard infant vaccines at 8 months of age for infants receiving maP plus HBV compared to infants receiving only HBV at birth.

Lower titers to other vaccines, but still in protective range. There was, however, significantly lower GMC to Hib, hepatitis B, diphtheria and tetanus antigens in the maP group. These lower concentrations were still above thresholds expected to be protective. Titers to PCV-13 antigens were not significantly different between groups.  

Bottom Line: Neonatally dosed maP vaccine appears safe while being immunogenic, and increases both the percent seropositive rate, as well as total titers to pertussis antigens. Perhaps all we needed was to drop the D and T components to get neonates to respond well to neonatally dosed pertussis antigens. The maP vaccine could be a useful part of our vaccine armamentarium, particularly for infants of mothers who had not received Tdap during pregnancy. Of course, such a vaccine is likely three to five years away, so in the meantime, maternal third trimester Tdap is our best tool to prevent severe pertussis in young infants.

 

References:

  1. Global Childhood Deaths from Pertussis: A Historical Review. Chow MY, Khandaker G, McIntyre P. Clin Infect Dis. 2016;63(suppl 4):S134-S141.
  2. Severe Pertussis in Infants: Estimated Impact of First Vaccine Dose at 6 versus 8 Weeks in Australia. Foxwell AR, McIntyre P, Quinn H, Roper K, Clements MS. Pediatr Infect Dis J. 2011;30(2):161-163.
  3. Poor Immune Responses to a Birth Dose of Diphtheria, Tetanus, and Acellular Pertussis Vaccine. Halasa NB, O’Shea A, Shi JR, LaFleur BJ, Edwards KM.  J Pediatr. 2008;153(3):327-332.
  4. Immunogenicity and Safety of Monovalent Acellular Pertussis Vaccine at Birth: A Randomized Clinical Trial. Wood N, Nolan T, Marshall H, Richmond P, Gibbs E, Perrett K, McIntyre P.  JAMA Pediatr 2018 172(11):1045-1052

Figure Footnote

Geometric mean concentrations (GMC) are represented as bars on the left axis and percent sero-response on the right axis. Hepatitis B GMC is in thousands of ELU to allow fit on axis comparable to other antigens.