Indian Pediatr 2017;54: 11-13
Hexavalent Vaccinations: The Future of
Department of Neonatology, St. John’s Medical College
Hospital, Bangalore, India.
s the world takes rapid strides in the
eradication of polio, the trivalent inactivated polio vaccine (IPV)
would be the only polio vaccine available in the near future. Since the
maintenance of herd immunity is important for sustaining polio
eradication, this vaccine would need to be used in the early childhood
immunization schedule for many years to come . WHO’s Strategic
Advisory Group of Experts (SAGE) group’s recommendation, that at least
one dose of inactivated polio vaccine (IPV) along with oral polio
vaccine (OPV) be administered to infants in countries currently using
OPV, has been incorporated in the current national immunization schedule
of India .
In India and other similar countries, the successful
implementation of IPV depends on many aspects of vaccine delivery,
including the availability of an effective and affordable vaccine.
Combination (multivalent) vaccines have the potential to simplify the
currently complex childhood immunization schedules, improve caregiver
compliance, and reduce healthcare costs. Hexavalent vaccines containing
Diphtheria (D), Tetanus (T), Pertussis (P), Hepatitis B (HBV),
Haemophilus influenzae B (Hib) and the three IPV antigens have been
considered logically and scientifically sound charioteers of such a
strategy, and have been touted to be the ultimate combination vaccine
for routine immunization . Another bugbear in the success of any
vaccination strategy (both public and private) is the high injection
density during infancy, which cannot be ignored. To illustrate, a child
gets as many as 21 injections within the first 2 years of life with the
currently available combination vaccines as per Indian Academy of
Pediatrics (IAP) recommendations . This number comes down only
slightly even if we exclude the pneumococcal vaccine. This leads to a
caregiver perception that their babies receive "too many shots too
soon," with vaccine hesitancy and the consequent effects including
deferred doses and decreased coverage rates . The use of combined
vaccines offers a number of potential benefits with regard to this
issue, including a reduction in the number of patient visits, reduced
complications associated with multiple intramuscular injections,
decreased costs of stocking and administering separate vaccines, and a
reduced risk of delayed or missed vaccinations. The use of combined
vaccines has been shown to improve vaccine coverage and timeliness .
The research paper by Chhatwal, et al. 
published in this edition of Indian Pediatrics evaluates the
efficacy of one such vaccine that is already approved in many countries,
and is being used in their national schedules. The authors demonstrate
very good seroconversion for all components even without a control
group, and show how it can be integrated into the current immunization
schedules. Moreover, the fully liquid preparations of hexavalent
vaccines have distinct advantages over those which require
reconstitution. Average preparation time is found to be almost half for
the fully-liquid vaccine compared the non-fully-liquid vaccine. In the
same study, almost all health care personnel (97.6%) stated that they
would prefer the use of the fully-liquid vaccine in their daily practice
Regarding pertussis vaccination, recent reports
suggest a waning of protective immunity in adolescence that might be
responsible for an increase in cases of pertussis in infants under six
months of age, before they are fully vaccinated . In high-income
countries, this waning immunity to pertussis is being addressed by
additional booster immunizations through the use of DTaP to replace DT
in older age groups. However, due to the higher cost, this is not
considered to be a viable option for lower-middle income countries like
India. WHO also observes the hypothesis that transition from wP (whole
cell pertussis) to aP (acellular pertussis) vaccines may be associated
with resurgence of disease. Though the licensed aP and wP vaccines have
equivalent efficacy in preventing disease in the first year of life,
there is a more rapid waning of protection, and possibly a reduced
impact on disease transmission, with aP compared to wP vaccines. It
states that a switch from wP to aP vaccines for primary infant
immunization should only be considered if the inclusion in the national
immunization schedules of additional periodic booster or maternal
immunization can be assured and sustained . Also, the IAP Advisory
Committee on Vaccines & Immunization Practices (ACVIP) recommends that
DTaP vaccine/combinations should preferably be avoided for the primary
series and if any acellular pertussis containing vaccine is used, it
must at least have three or more components in the product, which is not
the case in this investigational vaccine . Interestingly, no
hexavalent combinations with whole cell pertussis (wP) are commercially
available or in late-stage of development because of numerous technical
and logistical issues, and are unlikely to be available in next few
years . The classic wP vaccine with thimerosal also faces a major
challenge of incompatibility with IPV antigens. The production of these
vaccines is technically resource-intensive, which increases production
costs and therefore, many manufacturers target them as premium products.
Therefore, the hexavalent vaccines that are most likely to be available
now, or in the very near future are primarily intended and priced for
private markets. With regard to the newer Sabin IPV, although some
vaccine manufacturers have access to the Sabin strains (for OPV
product), further effort and time would be needed to develop an
inactivated form that is compatible for combination vaccine development
There have been a few issues with the combination
vaccines themselves in the past. Hexavac (Sanofi Pasteur MSD, Lyon,
France), which was licensed in Europe in 2000 as a pediatric primary and
booster immunization, was recommended for suspension of marketing
authorization by European Medicines Agency in September 2005 because of
the reduced immunization properties of the HBV component . However,
the newer vaccine from the same manufacturers – Hexyon or Hexaxim – has
a higher HBsAg content and uses a different method for its production.
This seems to have resulted in higher immunogenicity compared to hexavac
. A possible temporal association between first immunization with
hexavac and the occurrence of sudden unexpected death was also suspected
. This claim was strongly refuted on further investigation. The
other widely used hexavalent vaccine Infanrixhexa (GSK, Riixensart,
Belgium), which contains three pertussis antigens (PT, FHA and PRN), has
been demonstrated to be immunogenic, effective, safe and well tolerated
in children regardless of gestational age at birth, and not
significantly different from the vaccines used as comparators. The
immunogenicity seems superior to Hexavac for hepatitis B until 7–9 years
of age . Furthermore, vaccination with this DTaP-HBV-IPV/Hib in
infancy induces sustained seroprotection and immune memory against HBV
even in 12-13 year-old adolescents . The comparison of this vaccine
between two schedules in Indian infants has also been recently published
. With regards to the current study, the immunological response with
co-administration of PCV7 and rotavirus vaccine was not studied. Also,
the persistence of seroprotection, especially with pertussis (having two
antigens), and the effect of administration of a booster dose were not
In conclusion, these hexavalent formulations are
already a necessary component of the vaccination schedule, and would be
even more pertinent in the days ahead. However, they would need to be
monitored for long-term effectiveness in view of the growing concern of
waning immunity against diseases such as pertussis when using
acellular-pertussis vaccine, and possibly hepatitis B when using
Funding: None; Competing interest: None
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