MMWR Weekly May 22, 2009 / 58(19); 521-524

Description
This article describes important work carried out by the US Centers for Disease Control and Prevention (CDC) to assess the level of cross-reactive antibody titres to the new influenza A(H1N1) virus in children and adults before and after vaccination with ordinary seasonal influenza vaccines. The study is important because it provides information as to whether the current seasonal influenza vaccines containing ordinary A(H1N1) antigen might provide any protection ahead of the development of specific vaccines against the new influenza A(H1N1) virus.

Pre and post vaccination sera were provided to CDC by academic, government and industry partners. They consisted of serum specimens collected from healthy human participants before and after vaccination with two different types of vaccines: ordinary intramuscular seasonal trivalent inactivated influenza vaccine (TIV) and intranasal live attenuated influenza vaccine (LAIV) used in the USA mostly for children. The TIV vaccine used included that of the four seasons 2005-06 to 2008-09 whereas the LAIV vaccine was only for 2005-06 and 2006-07.

The viruses used for the vaccination tests were seasonal vaccines – including strains: 2005-06 & 2006-07 (A/New Caledonia/20/1999), 2007-08 (A/Solomon Islands/3/2006) and 2008-09 (A/Brisbane/59/2007). The novel influenza A(H1N1) virus used was A/California/04/2009. Antibody levels were determined by microneutralization (MN) and hemagglutination inhibition (HI) assays. The microneutralization test was preferred to assess cross-reactive antibody levels of A/California/04/2009 in populations before and after vaccination with seasonal influenza vaccines as it gave higher titres and more seroconversions were detected.

For sera from 79 children ranging in age from 6 months to 9 years, little evidence was found of any pre-vaccination cross-reactive antibodies to A/California/04/2009; and no such antibodies appeared after vaccination with both seasonal TIV and LAIV. However seroconversions for the seasonal vaccine strains were detected in 67%-100% of children.

In adults, vaccination with TIV resulted in seroconversions to the seasonal influenza A(H1N1) vaccine strain in 78% of adults aged 18-40 years and 54% of adults aged over 60 years. Whereas when the new A/California/04/2009 was tested, although there were some seroconversions, the titre achieved were fivefold to tenfold lower among all adults when comparing the postvaccination to prevaccination geometric mean titre (GMT) ratios.

However there were some important age differences in adults when it came to new A/California/04/2009. While only 6% of adults aged 18-40 years had prevaccination MN titres of equal to or over 1 in 160 the figure rose to 33% for adults of more than 60 years. In older adults prevaccination GMT of adults aged >60 years against the novel influenza virus was significantly higher than against the seasonal 2007-08 H1N1 vaccine.(1)

ECDC Comment (28-05-09)
These results are consistent with there being no protection from the current seasonal influenza vaccines against the new influenza A(H1N1) virus despite the former containing another A(H1N1) virus. This emphasises the different genetic composition of the new influenza A(H1N1) virus from most other influenza viruses in humans and a substantial degree of genetic divergence between the new influenza A(H1N1) virus and human seasonal influenza viruses.(2) Indeed this paper is the scientific basis for the statements that current seasonal vaccines offer little prospect of protecting against the new influenza A(H1N1) virus. What is more intriguing is the suggestion of cross-reactivity in at least some older people. It is important to emphasise here that cross-reactivity does not equal protection. However in previous pandemics some indication of protection in older people has been found and attributed to exposure to antigenically similar viruses in the distant past.(3) This is especially interesting here in that there has been some comments on under-representation of older people in the cases in the USA. Whether this represents immunity or simply that the new virus has yet to reach that age-group remains to be seen but its an important are of work for prioritising use of pandemic vaccine and prevention and mitigation strategies

1. CDC Serum Cross-Reactive Antibody Response to a Novel Influenza A (H1N1) Virus After Vaccination with Seasonal Influenza Vaccine MMWR May 22, 2009 / 58(19);521-524  

2. Garten RJ, Davis Ct, Russell CR et al. Antigenic and genetic characteristics of swine origin 2009 A(H1N1) influenza viruses circulating in humans. Science Experss 22 May 2009. 10.1126/science.1176225

3. Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis [serial on the Internet]. 2006 Jan [date cited]. Available from 

4. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team the article was published at NEJM.org on May 7, 2009. N Engl J Med 2009;360 (10.1056/NEJMoa0903810)