Yonsei Med J.  2013 Mar;54(2):271-282. 10.3349/ymj.2013.54.2.271.

Cross-Protective Immune Responses Elicited by Live Attenuated Influenza Vaccines

• Jang YH
• Seong BL

• KMID: 1503885
• DOI: http://doi.org/10.3349/ymj.2013.54.2.271

Abstract

The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.

Keyword

Influenza live attenuated vaccine; cross-protection; cold-adaptation; universal vaccine

MeSH Terms

Adaptive Immunity
Antigens, Viral/immunology
*Cross Protection
Genome, Viral
Humans
Immunity, Innate
Influenza Vaccines/*immunology/therapeutic use
Influenza, Human/*prevention & control
Orthomyxoviridae/genetics/immunology
Vaccines, Attenuated
Antigens, Viral
Influenza Vaccines
Vaccines, Attenuated

Figure

• 

  Fig. 1 T cell Immunodominance. Virus-specific CTLs recognize the complex of the viral peptide and MHC class-I molecule presented on the membrane of the infected cells. Some peptides generate strong signals and thereby lead to the robust clonal expansion of the responding CTLs (immunodominant), some generate weak (subdominant) signals, and others barely generate a signal (cryptic) only detectable in the absence of the others. The hierarchy of the T cell immunodominance shaped by primary exposure to a virus varies upon a subsequent infection with heterologous virus. CTL, cytotoxic T lymphocyte; TCR, T cell receptor; MHC, major histocompatiblity complex.

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