Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.
OBJECTIVE
To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants.


METHODS
A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE.


RESULTS
The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain.


CONCLUSIONS
RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.
Araujo
Eliete C
EC
Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde, Belém, PA, Brasil.
Clemens
Sue Ann C
SA
Oliveira
Consuelo S
CS
Justino
Maria Cleonice A
MC
Rubio
Pilar
P
Gabbay
Yvone B
YB
da Silva
Veronilce B
VB
Mascarenhas
Joana D P
JD
Noronha
Vânia L
VL
Clemens
Ralf
R
Gusmão
Rosa Helena P
RH
Sanchez
Nervo
N
Monteiro
Talita Antônia F
TA
Linhares
Alexandre C
AC
D000914:Antibodies, Viral / Q000097:blood*; D001938:Brazil; D004311:Double-Blind Method; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007223:Infant; D008800:Mexico; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines; D012720:Severity of Illness Index; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D014687:Venezuela
D000914:Antibodies, Viral; C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated