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Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-control study in Mexico City

BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b3928 (Published 06 October 2009) Cite this as: BMJ 2009;339:b3928

Clinical efficiency after one dose of Pandemrix in Norway

There is ongoing debate whether previous vaccine-induced immunity
against seasonal flu may provide some protection against pandemic A(H1N1)
flu (1,2). Linked to this question is the issue how fast clinical
protection may be attained with the new vaccines against pandemic flu.
Textbook knowledge is that serum antibody levels peak 2-4 weeks after
vaccination in primed, healthy individuals (3). For unprimed individuals,
children, elderly and the immunosuppressed it is expected that more than
one dose of vaccine may be necessary and that it may take longer time to
attain immunity.

In Norway a mass vaccination campaign against pandemic A(H1N1) flu
started 19 October 2009. So far 1.7 million adult doses of inactivated,
adjuvanted vaccine (Pandemrix, produced by GlaxoSmithKline) have been
distributed in a population of 4.8 million people. The number of doses
administered is unknown. For the first 4 weeks of the campaign the
vaccines were given to defined risk groups and to health workers with
direct patient contact. Children between 6 months and 10 years were given
one half of the adult dose. It was decided to withhold the second dose
until all Norwegians have been offered one dose of the pandemic vaccine.
From the first day of the campaign, each given dose could be linked to a
vaccinee on the basis of unique personal numbers of each Norwegian
inhabitant. Data were often entered after a certain lag period, and
currently the vaccine registry contains data on pandemic flu vaccine for
about 700 000 people. The vaccine registry does not yet contain data on
vaccination against seasonal flu.

Norway was struck hard by flu during the second half of October and
the first half of November 2009. By use of a sentinel data system it was
estimated that 300 000 Norwegians were infected during week 45. This was
the highest influenza figure recorded during a week since registration
started 15 years ago. Only 1 per cent of the cases were laboratory
verified due to laboratory restraint. Testing was essentially done for
patients with serious symptoms and to people co-residing with risk-group
individuals.

Patients with laboratory verified flu are routinely reported to the
National Institute of Public Health. By the end of week 48 (29 November
2009) 105 persons were reported with laboratory verified influenza A(H1N1)
in spite of vaccination. The Table gives numbers of vaccine doses
distributed and numbers of new flu cases among vaccinees per week.
Complete information for the dates of both vaccination and first symptoms
were available for 91 of the 105 reports.

The great majority of the 91 vaccinees identified in our data set
came down with laboratory verified flu just a few days after vaccination.
Two patients were vaccinated by mistake after the disease had occurred. 47
vaccinees had their first symptoms between day 0 and day 4, and twenty
eight vaccinees had their first symptoms between day 5 and day 9. Eight
vaccinees had their first symptoms between day 10 and day 14 after
vaccination and only six vaccinees had first symptoms after 14 days. Some
characteristics of the patients were given on the written reports. 10 of
the 14 vaccinees with the first day of symptoms later than day 10 after
vaccination belonged to groups that were scheduled for a second vaccine
dose (8 children below ten years of age and 2 immunosuppressed patients).
The four remaining “vaccine failures” comprised one pregnant woman, one
child who had just experienced its tenth birthday, one patient with
chronic asthma, and one elderly person exposed to massive transmission of
flu from three other family members.

This study clearly has limitations, and valid statistical calculation
of vaccine efficiency cannot be made. However, the data indicate that
during a period of intense transmission few vaccinees contracted
laboratory verified influenza A(H1N1) later than 9 days post vaccination.
Hence, in our population the pandemic vaccine performed similar to
efficacious vaccines against seasonal flu in seasons with a good fit
between vaccine and virus strain (3). One dose of pandemic vaccine may
provide sufficient protection for immunocompetent adults, but two doses
seem to be necessary for children under the age of ten years and for
immunosuppressed people. One of the primary aims of the continued
surveillance in Norway will be to investigate possible waning of immunity
after one, respectively two doses of pandemic vaccine.

Svenn-Erik Mamelund, Senior Adviser, PhD, Norwegian Institute of
Public Health, Div. of Infectious Disease Control, Vaccine department, PO
Box 4404 Nydalen, NO-0403 Oslo, Norway

Svenn-Erik.Mamelund@fhi.no

Jann Storsæter, Senior Physician, PhD, Norwegian Institute of Public
Health, Div. of Infectious Disease Control, Vaccine department, PO Box
4404 Nydalen, NO-0403 Oslo, Norway

Inger Lise Haugen, Adviser, Norwegian Institute of Public Health, Div. of
Infectious Disease Control, Vaccine department, PO Box 4404 Nydalen, NO-
0403 Oslo, Norway

Maren Stapnes Ege, Senior Adviser, Norwegian Institute of Public Health,
Div. of Infectious Disease Control, Vaccine department, PO Box 4404
Nydalen, NO-0403 Oslo, Norway

Marianne A. Rise Bergsaker, Senior Physician, Norwegian Institute of
Public Health, Div. of Infectious Disease Control, Vaccine department, PO
Box 4404 Nydalen, NO-0403 Oslo, Norway

1. Garcia-Garcia L, Valdespino-Gómez JL. BMJ 2009;339:b4978

2. Serum cross-reactive antibody response to a novel influenzae A(H1N1)
virus after vaccination with seasonal influenzae vaccine. MMWR Morb Mortal
Wkly Rep 2009;58:521-4

3. Bridges CB et al. Inactivated influenza vaccines. In: Plotkin S,
Orenstein W, Offit P. editors. Vaccines. 5th edition. Elsevier; 2008. p.
259-290.

Competing interests:
None declared

Competing interests: No competing interests

01 December 2009
Svenn-Erik Mamelund
Senior Adviser, PhD
Jann Storsæter, Inger Lise Haugen, Maren Stapnes Ege, and Marianne A. Rise Bergsaker
Norwegian Institute of Public Health, Dept of Vaccines, PO Box 4404 Nydalen, NO-0403 Oslo, Norway