Concomitant administration of a liquid formulation of human rotavirus vaccine (porcine circovirus-free) with routine childhood vaccines in infants in the United States: Results from a phase 3, randomized trial. Issue 10 (5th March 2021)

• Record Type: Journal Article
• Authors: Abu-Elyazeed, Remon; Klein, Nicola P.; Moerman, Leentje; Povey, Michael; Pruitt, Anthony; Senders, Shelly; Silas, Peter; Bi, Dan; Acevedo, Armando; Amisola, Rogelio; Anschutz, Luke; Bataille, Regine; Campbell, James; Cornish, Matthew; Domachowske, Joseph; Fling, John; Franklin, Earl; Fuller, Joshua; Gabrielsen, Alvin; Garscadden, Alan; Guido, Giancarlo; Hedrick, James; Hurley, David; Hurley, Donald; Johnston, William; Kulshrestha, Aarti; Leonardi, Michael; Levinson, Martin; Livingston, Sean; Marshall, Gary; Pirrotta, Paola; Rok, Walter; Russell, Stephen; Schear, Martin; Shepard, Julie; Sigg, Laurent; Singh, Tina; Tipton, Mary; Ugarte, Ana; Wisman, Paul; Zissman, Edward;
• Is Part Of: Vaccine. Volume 39:Issue 10(2021)
• Page Start: 1534
• Page End: 1543
• Publication Date: 2021-03-05
• Subjects: Human rotavirus vaccine -- Porcine virus-free rotavirus vaccine -- Routine childhood vaccines -- Concomitant administration -- Non-inferiority; ACIP Advisory Committee on Immunization Practices -- AE adverse event -- ANOVA analysis of variance -- CI confidence interval -- D diphtheria -- DTaP-HBV-IPV diphtheria-tetanus-acellular pertussis, hepatitis B and inactivated poliovirus combination vaccine -- ED50 median effective dose -- ES exposed set -- GMC geometric mean concentration -- GMT geometric mean titer -- HBs antibodies hepatitis B surface antibodies -- Hib Haemophilus influenzae type b -- Hib-TT monovalent tetanus toxoid-conjugated vaccine against Hib -- HBRV human-bovine reassortant vaccine -- HRV live-attenuated human rotavirus vaccine -- IgA immunoglobulin A -- IU international units -- Liq liquid -- Lyo lyophilized -- OPV oral poliovirus vaccine -- PCV porcine circovirus -- PVC13 13-valent pneumococcal conjugate vaccine -- PRP polyribosyl-ribitol-phosphate -- PnPS pneumococcal capsular polysaccharide -- PPS per-protocol set -- RV rotavirus -- SAE serious adverse event -- T tetanus -- U units -- US United States; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2020.08.070
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: A porcine circovirus-free human rotavirus vaccine (PCV-free HRV) has been developed. We compared routine vaccines coadministration with liquid PCV-free vs lyophilized HRV. We showed non-inferior immune responses for coadministration with PCV-free HRV vs HRV. We observe comparable safety profiles for liquid PCV-free HRV and lyophilized HRV. Liquid PCV-free HRV could be used as part of routine vaccination in United States. Abstract: Background: In response to the detection of porcine circovirus type 1 (PCV-1) in the human rotavirus vaccine (HRV), a PCV-free HRV (no detection of PCV-1 and PCV-2 according to the detection limit of tests used) was developed. Liquid (Liq) PCV-free HRV previously showed immunogenicity and safety profiles comparable to lyophilized (Lyo) HRV. Methods: This was a phase 3a, randomized, single-blind study (NCT03207750) conducted in the United States. Healthy infants aged 6–12 weeks received 2 doses (0, 2 months) of either Liq PCV-free HRV or Lyo HRV with routine vaccines (0, 2, 4 months): diphtheria-tetanus-acellular pertussis, hepatitis B and inactivated poliovirus combination vaccine (DTaP-HBV-IPV), monovalent tetanus toxoid-conjugated vaccine against Haemophilus influenzae type b (Hib-TT), and 13-valent pneumococcal conjugate vaccine. Co-primary objectives were: (i) to assess non-inferiority of immune responses to routine vaccine antigens 1 month post-dose 3 following co-administration with Liq PCV-free HRV compared to Lyo HRV; (ii) to rule out a 10% decrease in seroresponse to pertussis antigens after dose 3. Other objectives were to evaluate immunogenicity and safety of HRV vaccines. Results: Of 1272 vaccinated infants, 990 (489 in Liq PCV-free HRV and 501 in Lyo HRV group) were included in the per-protocol set. All statistical criteria were met, thus co-primary objectives were demonstrated. Seroprotection/seropositivity rates in both groups were high: 100% for diphtheria/tetanus, ≥99.3% for HBV, ≥99.8% for polio, ≥99.8% for each pertussis antigen, ≥90.8% for all pneumococcal serotypes except serotype 3 (≥69.1%), and ≥ 97.4% for Hib. Most infants seroconverted for anti-RV antibodies (76.3% of Liq PCV-free HRV and 78.9% of Lyo HRV recipients). Geometric mean concentrations/titers were comparable between groups. Incidences of adverse events and serious adverse events were similar between groups. Conclusion: Routine pediatric vaccines co-administered with Liq PCV-free HRV showed non-inferior immune responses and similar safety profiles to those following co-administration with Lyo HRV.