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Inducing Quality Immune Response to Respiratory Viruses May Not Be a Simple Task


Affiliations
1 HIV-AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur (PO), Bengaluru 560 064, India
 

A few front-runner vaccines for COVID-19 have reported over 90% protection in phase II/III clinical trials, raising hopes. These studies, however, have evaluated only a relative, not absolute, protection. The leading COVID-19 vaccines have been designed to elicit a systemic, not mucosal, immune response. While a systemic immune response may reduce disease severity, only the mucosal immune response can reduce the spreading of a respiratory viral infection. Here, we explain why inducing long-lasting and high-quality immune response to mucosal infections is typically challenging. A few possible solutions are proposed.

Keywords

COVID-19 Vaccines, Clinical Trials, Respiratory Viral Infection, Systemic and Mucosal Immune Response.
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  • Amanna, I. J. and Slifka, M. K., Successful vaccines. Curr. Top. Microbiol., 2020, 428, 1–30.

  • Thursby, E. and Juge, N., Introduction to the human gut microbiota. Biochem. J., 2017, 474(11), 1823–1836.

  • Hammarlund, E., Lewis, M. W., Hanifin, J. M., Mori, M., Koudelka, C. W. and Slifka, M. K., Antiviral immunity following smallpox virus infection: a case-control study. J. Virol., 2010, 84(24), 12754–12760.

  • Cevik, M., Kuppalli, K., Kindrachuk, J. and Peiris, M., Virology, transmission, and pathogenesis of SARS-CoV-2. Br. Med. J., 2020, 371, 3862.

  • Hilleman, M. R., Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections. Proc. Natl. Acad. Sci. USA, 2004, 101(Suppl 2), 14560–14566.

  • Mowat, A. M., To respond or not to respond – a personal perspective of intestinal tolerance. Nature Rev. Immunol., 2018, 18(6), 405–415.

  • Holt, P. G., Strickland, D. H., Wikström, M. E. and Jahnsen, F. L., Regulation of immunological homeostasis in the respiratory tract. Nature Rev. Immunol., 2008, 8(2), 142–152.

  • Moreno-Fierros, L., García-Silva, I. and Rosales-Mendoza, S., Development of SARS-CoV-2 vaccines: should we focus on mucosal immunity? Exp. Opinion Biol. Therapy, 2020, 20(8), 831–836.

  • Hwang, J. Y., Randall, T. D. and Silva-Sanchez, A., Inducible Bronchus-associated lymphoid tissue: taming inflammation in the lung. Front. Immunol., 2016, 7, 258.

  • Corthésy, B., Multi-faceted functions of secretory IgA at mucosal surfaces. Front. Immunol., 2013, 4, 185.

  • Allie, S. R., Bradley, J. E., Mudunuru, U., Schultz, M. D., Graf, B. A., Lund, F. E. and Randall, T. D., The establishment of resident memory B cells in the lung requires local antigen encounter. Nature Immunol., 2019, 20(1), 97–108.

  • Wagner, D. K., Clements, M. L., Reimer, C. B., Snyder, M., Nelson, D. L. and Murphy, B. R., Analysis of immunoglobulin G antibody responses after administration of live and inactivated influenza A vaccine indicates that nasal wash immunoglobulin G is a transudate from serum. J. Clin. Microbiol., 1987, 25(3), 559– 562.

  • Vonarburg, C. et al., Topical application of nebulized human IgG, IgA and IgAM in the lungs of rats and non-human primates. Respir. Res., 2019, 20(1), 99.

  • Holmgren, J. and Czerkinsky, C., Mucosal immunity and vaccines. Nature Med., 2005, 11(4), S45–S53.

  • Valtanen, S., Roivainen, M., Piirainen, L., Stenvik, M. and Hovi, T., Poliovirus-specific intestinal antibody responses coincide with decline of poliovirus excretion. J. Infect. Dis., 2005, 182(1), 1–5.

  • Buisman, A. M., Abbink, F., Schepp, R. M., Sonsma, J. A., Herremans, T. and Kimman, T. G., Preexisting poliovirus-specific IgA in the circulation correlates with protection against virus excretion in the elderly. J. Infect. Dis., 2008, 197(5), 698–706.

  • Clarke, E. and Desselberger, U., Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings. Mucosal Immunol., 2015, 8(1), 1–17.

  • Baker, J. M., Tate, J. E., Leon, J., Haber, M. J., Pitzer, V. E. and Lopman, B. A., Postvaccination serum antirotavirus immunoglobulin A as a correlate of protection against rotavirus gastroenteritis across settings. J. Infect. Dis., 2020, 222(2), 309–318.

  • Jin, C. et al., Vi-specific serological correlates of protection for typhoid fever. J. Exp. Med., 2020, 218(2), e20201116.

  • Harris, J. B., Cholera: immunity and prospects in vaccine development. J. Infect. Dis., 2018, 218(3), S141–S146.

  • Masomian, M., Ahmad, Z., Ti Gew, L. and Poh, C. L., Development of next generation Streptococcus pneumoniae vaccines conferring broad protection. Vaccines, 2020, 8(1), 132.

  • Ruckwardt, T. J., Morabito, K. M. and Graham, B. S., Immunological lessons from respiratory syncytial virus vaccine development. Immunity, 2019, 51(3), 429–442.

  • Krammer, F., The human antibody response to influenza A virus infection and vaccination. Nature Rev. Immunol., 2019, 19(6), 383–397.

  • Brandtzaeg, P., Role of mucosal immunity in influenza. Dev. Biologic., 2003, 115, 39–48.

  • Waffarn, E. E. and Baumgarth, N., Protective B cell responses to flu – no fluke. J. Immunol., 2011, 186(7), 3823–3829.

  • Vogel, A. B. et al., Immunogenic BNT162b vaccines protect rhesus macaques from SARS-COV-2. Nature, 2021; doi:10.1038/s41586-021-03275-y

  • Corbett, K. S. et al., Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med., 2020, 383(16), 1544–1555.

  • van Doremalen, N. et al., ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature, 2020, 586, 578–582.

  • Guebre-Xabier, M. et al., NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge. Vaccine, 2020, 38(50), 7892–7896.

  • Mercado, N. B. et al., Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature, 2020, 586(7830), 583– 588.

  • Baden, L. R. et al., Efficacy and safety of the mRNA-1273 SARSCoV2 vaccine. N. Engl. J. Med., 2020, 384(5), 403–416.

  • Polack, F. P. et al., Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Eng. J. Med., 2020, 383(27), 2603–2615.

  • Doshi, P., Will COVID-19 vaccines save lives? Current trials aren’t designed to tell us. Br. Med. J., 2020, 371: m4037; https://pubmed.ncbi.nlm.nih.gov/33087398

  • Voysey, M. et al., Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet, 2021, 397(10,269), 99–111.

  • Logunov, D. Y. et al., Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet, 2021, 397, 671–681.

  • Lauring, A. S. and Hodcroft, E. B., Genetic variants of SARSCoV2 – what do they mean? J. Am. Med. Assoc., 2021, 325(6), 529–531.

  • Moore, J. P. and Offit, P. A., SARS-CoV-2 vaccines and the growing threat of viral variants. J. Am. Med. Assoc., 2021, 325(9), 821– 822.

  • Horwitz, M. A., Jia, Q. A., Bielefeldt-Ohmann, H., Maison, R., Maslesa-Galic, S. and Bowen, R. A., Replicating bacteriumvectored vaccine expressing SARS-CoV-2 membrane and nucleocapsid proteins protects against severe COVID-19 disease in hamsters. bioRxiv, 2020.

  • Couch, R. B. and Kasel, J. A., Immunity to influenza in man. Annu. Rev. Microbiol., 1983, 37, 529–549.

  • Tomar, J., Born, P. A., Frijlink, H. W. and Hinrichs, W. L., Dry influenza vaccines: towards a stable, effective and convenient alternative to conventional parenteral influenza vaccination. Expert Rev. Vaccines, 2016, 15(11), 1431–1447.

  • Boyaka, P. N., Inducing mucosal IgA: a challenge for vaccine adjuvants and delivery systems. J. Immunol., 2017, 199(1), 9–16.

  • Pallesen, J. et al., Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl. Acad. Sci. USA, 2017, 114(35), E7348–E7357.


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  • Inducing Quality Immune Response to Respiratory Viruses May Not Be a Simple Task

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Authors

Udaykumar Ranga
HIV-AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur (PO), Bengaluru 560 064, India
Mangaiarkarasi Asokan
HIV-AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur (PO), Bengaluru 560 064, India

Abstract


A few front-runner vaccines for COVID-19 have reported over 90% protection in phase II/III clinical trials, raising hopes. These studies, however, have evaluated only a relative, not absolute, protection. The leading COVID-19 vaccines have been designed to elicit a systemic, not mucosal, immune response. While a systemic immune response may reduce disease severity, only the mucosal immune response can reduce the spreading of a respiratory viral infection. Here, we explain why inducing long-lasting and high-quality immune response to mucosal infections is typically challenging. A few possible solutions are proposed.

Keywords


COVID-19 Vaccines, Clinical Trials, Respiratory Viral Infection, Systemic and Mucosal Immune Response.

References





DOI: https://doi.org/10.18520/cs%2Fv120%2Fi8%2F1315-1323