Immunogenicity and safety of Takeda’s tetravalent dengue vaccine (TDV) in healthy children in Asia and Latin America (Lancet Infect Dis.　2018;18:162-70).

In a multi-center cluster randomized trial of two vs three doses of quadrivalent　human papilloma virus (qHPV) vaccine in India, suspension of the vaccination led to per protocol and partial vaccination of 10-18/ year old girls leading to four　study　groups, two by design and two by default. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one　dose. One　dose　recipients demonstrated a robust and sustained immune response against　HPV　16 and 18, albeit inferior to that of 3- or 2-doses, and the antibody levels were stable over a 4-year period. The frequencies of cumulative incident and persistent　HPV　16 and 18 infections up to 7-years of follow-up were similar and uniformly low in all the vaccinated　study　groups; the frequency of　HPV　16 and 18 infections were significantly higher in unvaccinated age-matched control women than among　vaccine　recipients. The researchers conclude that a　single　dose　of HPV　vaccine　is immunogenic and provides lasting protection against　HPV　16 and 18 infections similar to the three- and two-dose　vaccine　schedules.

Comments: The single-dose schedule would not only be more economical but would have programmatic advantages over multiple-dose schedule. Though the above study has some limitations like the participants were not randomized nor blinded to the number of doses received, the distribution of the participants by the study sites was different across the vaccinated dose groups. In fact, the trial was not designed in the first place to prospectively assess the effectiveness of one-dose of HPV vaccine. Nevertheless, this trial has significant number of participants (around 5000) than other single dose trials. More trials with longer follow-ups on HPV　infection and　cervical　precancerous lesions are needed before single-dose schedule replace the existing ones.

Immunogenicity and safety of a novel liquid hexavalent DTwP-Hib/Hep B-IPV vaccine to licensed combination vaccines in healthy infants (Vaccine. 2018;36:2378-84).

Immunogenicity and safety of a newly developed liquid DTwP-Hib/HepB-IPV hexavalent vaccine (EasySix) was evaluated and compared with administration of licensed Pentavac SD (DTwP-HepB/Hib) and Imovax Polio (IPV) vaccine among 284 participants, aged 6–10 weeks in an open-label, randomized multi-centric trial.

Post-vaccination, seroprotection was achieved against all six vaccine antigens in both vaccine groups. The seroresponse rate and antibody titers for all vaccine components were comparable between two groups. Both vaccines had similar reactogenicity profiles and were well tolerated; all adverse events resolved completely without any sequelae. Only one serious adverse event was reported that completely resolved; it was regarded unconnected to the vaccine administered. This study demonstrated that immunogenicity and safety profiles of this new combination vaccine are non-inferior to the commercially available vaccines.

Comments: This combination vaccine is the only available hexavalent vaccine employing whole-cell pertussis (wP) antigen in Indian market. Though the reported seroconversion rates for the pertussis component was slightly lower (around 68% and 76% for pertussis IgG and anti-PT, respectively) than other antigens, but was comparable to the comparator vaccine’s figures. In an earlier trial of a pentavalent vaccine from the same manufacturer, almost similar titers were reported for the pertussis component (65% and 72%). However, relying solely on immunogenicity data for pertussis efficacy/protection would not be an ideal way since till date no known single correlate of protection for pertussis exists, nor any established protective antibody levels are known.