Influenza A (H1N1) Blog

I received a comment from Paulo Amaral with amazing questions, leading me to advance this post. As follows, you can find the questions and the answer explaining what is relevant:

Would the annual vaccination against flu be liable for the low number of reports in elders?

What is the efficacy of the vaccine produced by mettles of A/Solomon Islands/3/2006 (H1N1), A/Brisbane/10/2007 (H3N2) and A/South Dakota/6/2007 (flu vaccine), mainly related to “crossed protection”?

I believe that it genetically produces a first protection barrier, provided that the current virus presents similar surface hemagglutinin and neuraminidase.

Initially, a briefing about the over than 90 years period that H1N1 lives between us and the importance of rearrangement and immunity:

Among, maybe, since 1906 in pigs and humans, the H1N1 1918 virus was an aviary virus [1]. By the time it was spread worldwide in two waves, one in March (Spring in the North Hemisphere) lighter, and another one in August (Fall)*, it killed about 50 million people worldwide, a number which is higher than the deaths verified in the First World War and due to any other disease within such a short period. Different from any other kind of flu up to now, the 1918 flu killed about 2,5% of the persons infected and reached, mainly, the young ones. While the seasonal flu kills the inmunosuppressed, very young children which still did not have any contact with the flu and elders which no longer have a well sustained immune response, 1918’s mettle killed many persons of ages between 20 and 35 years old.

At least one more wave occurred in later period, but it did not reach the same seriousness. Ever since, H1N1 virus circulates among the human population. It causes the annual flu by mutating its external proteins, the Hemagglutinin and Neuraminidase (HA and NA), enough to survive the collective immunity. In 1957, however, the virus had a new action. It suffered a reassortment, mixing its genes with the aviary virus’ and acquired, further to the PB1 gene, the new HA and NA. Keep this information and notice how recurring it will be.

With these new surface proteins the virus was no longer recognized by the antibodies and caused a pandemic, the Asian Flu. As the new Hemagglutinin and Neuraminidase were no longer recognized by the antibodies under virus inactivation tests, the old ones became known as H1 and N1 and these, received the denomination of H2 and N2.

H2N2 continued to circulate among the population until 1968, when a big reassortment occurred again. Once again, the PB1 and HA aviary genes entered within the human population. The new HA was not recognized by our immune system, and the virus caused another pandemic. The new HA was not either H1 or H2 and became known as H3. This H3N2 circulates up to now, currently between us, together with the H1N1 of 1951, which was reintroduced to the human race in 1977, probably by means of vaccine tests. The 26 years the H1N1 stayed out, replaced by the H2N2, were enough for the outbreak of one more generation of susceptible individuals.

As follows there is a summary of our Influenza’s history, as well as the swine, aviary and human viruses, which contributed for the current H1N1 [2]. Notice that the swine virus suffered a reassortment with the human and aviary viruses, what caused the confusion of the first analysis made with the 2009 California mettles (so called swine flu). The origin of the virus was believed to be swine and/or human, and it is the case, but in its background:

Have you notice the pattern? The virus, periodically, is reassorted and acquires new HA and NA, precisely the proteins that our immune system recognize quickly. Thus, the new virus is original for the population or, at least, partially.

But, what is the role of the prior immunity on the population?

According to Palese and coworkers, the prior immunity had its role, including in the 1918’s pandemic [3], contrary to the idea that the higher mortality in youngsters has been caused by an over response of the immune system. They argument that the W shaped age curve – with children, youngsters and elders among the most affected – is an effect of the elders immunity.

Among a population that has never exposed to a virus, its trend is to cause a great number of deaths in a V curve, killing very young children and adults and elders in higher numbers. The immune response of children between 5 and 14 years old is used to protect them more than the others. It was the occurrence in the Faroe Islands with the arrival of measles in 1846, smallpox brought by the Spanish to the Americas.

It was what happened with the Eskimos that died in 1918, which, until then, had never contracted the flu, since the frequent contact with modern civilization which had just started, had the highest mortality. In many tribes, only a few children survived. According to Palese, the Spanish Flu didn’t kill more adult and elder individuals just because they had already been exposed, few years before, to a similar virus, probably before the 1889 pandemic:

What about the current virus?

As we can see in the first figure, the current virus received new HA and NA. The swine virus’ H1 is present among the pigs since 1918 and was reassorted with a human virus and another aviary virus. The NA of the European swine virus of aviary origin also rearranged. Then:

What is the efficacy of the vaccine produced by mettles of A/Solomon Islands/3/2006 (H1N1), A/Brisbane/10/2007 (H3N2) and A/South Dakota/6/2007 (vaccine against flu), specially related to the “crossed protection”?

Very low, since this virus contains new HA and NA. There is some immune reaction, provided that we may classify them as H1 and N1, however, it is not enough for protection. Even though, remains a question:

Would the annual vaccination against flu, be liable for the shortage in the number of reports about elders?

It is possible that the shortage of the reports in elders is caused by a previous exposition, original to the newer generations. Something like what happened in 1918. For how long is our immune system able to recognize an already found virus? Apparently, for its whole life. At least, it is what occurs with nonagenarians that survived the Spanish Flu, who, even currently, more than 90 years later, have inactivating antibodies against that virus [4].Is there an immune response by the elders for the current swine H1N1?

The answer is… yes! According to the CDC, 1/3 of the samples of persons older than 60, collected between 2005 and 2009 hold antibodies which are reactive against this Influenza. Against less than 10% of the persons between 18 and 64 years old and none of the children tested [5]. If it would be the case that the prior vaccines provide the mentioned protection, such answer would be found in persons that received the vaccine, regardless the age range. Besides, children are among those receiving the vaccine every year.

It is not the case to exclude the elders from the candidates to the new vaccine, since this immunity was verified in vitro but not in vivo, however, it helps us to understand the dynamics of this virus, with which we lived for so long.

* we may not be sure if the same virus caused both the waves, provided the only virus samples we have belong to victims that died in the Winter but, as we didn’t find traces of other circulating viruses even in pigs, it is unlikely that it could be a different virus.

Still, the final part of the comment was left to the end, as the answer to be provided by me is my own opinion, without a direct bibliographyc reference:

Wouldn’t the PNEUMOCOCIC vaccination be recommended now? Since further protection (even knowing there is no 100% efficacy) against the pneumococic pneumonia (bacteria Streptococcus pneumonia, provided it would act as opportunistic infection, generating the aggravation of the patient’s conditions) and pneumococic bacteremia, it also protects against septicemia.

In this point, Paulo refers to the vaccine against pneumonia, one of the troubles of the common flu that may cause death. I believe it would not be the case, for several reasons: vaccine is regularly distributed to children, and I believe that the annual production is not sufficient for the immunization of a great portion of the population as a prevention form; to vaccinate only the contaminated individuals is not effective, due to the time required for us to develop an immune response; since it is a bacteria, it may be treated with antibiotics, a very efficient measure upon a timely made diagnosis.

Sources:

[1]Smith, G., Bahl, J., Vijaykrishna, D., Zhang, J., Poon, L., Chen, H., Webster, R., Peiris, J., & Guan, Y. (2009). From the Cover: Dating the emergence of pandemic influenza viruses Proceedings of the National Academy of Sciences, 106 (28), 11709-11712 DOI: 10.1073/pnas.0904991106
[2] Morens, D., Taubenberger, J., & Fauci, A. (2009). The Persistent Legacy of the 1918 Influenza Virus New England Journal of Medicine, 361 (3), 225-229 DOI: 10.1056/NEJMp0904819
[3] Palese, P., Tumpey, T., & Garcia-Sastre, A. (2006). What Can We Learn from Reconstructing the Extinct 1918 Pandemic Influenza Virus? Immunity, 24 (2), 121-124 DOI: 10.1016/j.immuni.2006.01.007
[4] Yu, X., Tsibane, T., McGraw, P., House, F., Keefer, C., Hicar, M., Tumpey, T., Pappas, C., Perrone, L., Martinez, O., Stevens, J., Wilson, I., Aguilar, P., Altschuler, E., Basler, C., & Jr, J. (2008). Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors Nature, 455 (7212), 532-536 DOI: 10.1038/nature07231
[5] Centers for Disease Control and Prevention (CDC) (2009). Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR. Morbidity and mortality weekly report, 58 (19), 521-4 PMID: 19478718