Unnatural immunity

REVIEW ARTICLE

Barman, Soni et al.

Precision Vaccine Development: Cues From Natural Immunity

Front. Immunol., 10 February 2022

Sec. T Cell Biology

Volume 12 - 2021

DOI: https://doi.org/10.3389/fimmu.2021.662218

EXCERPTS

Bordetella pertusis (BP), whooping cough

• "Despite the routine immunization with whole cell pertussis (wP) and acellular pertussis (aP) vaccine, pertussis remains resurgent."

• "Emergence of BP infection in the US population was dramatically reduced (99%) by the introduction of alum containing wP vaccine in 1950s (123, 124). In the USA during mid 1990s, alum-formulated aP replaced wP based formulations. The main driving factor was the desire to further reduce the rare incidents of febrile seizures in infants post vaccination, while nearly always recoverable, were associated with wP induced local and systemic reactogenicity (124, 125). The formulation of alum adjuvanted Diphtheria and Tetanus Toxoids along with Acellular Pertussis (DTaP) vaccine is variable, ranging from a mixture of virulence factors like PT alone or with FHA, PRN and/or fimbriae serotypes (FIM 2/3) (112, 126, 127). Despite successful DTaP vaccination, resurgence of pertussis was observed in developed countries in the first decade of 21st century (128). Lower efficacy and waning immunity in response to DTaP has become a major concern (129)."

Lessons From Influenza Infection and Future Vaccine Strategies

• "Development of a “universal vaccine” for influenza is challenging because seasonal vaccines lack efficacy against most circulating influenza strains due to antigenic variability. One of the current approaches for influenza vaccine development is to mimic the natural exposure via attenuated viral infection or viral vector administration which triggers natural immunity. Live attenuated licensed vaccine FluMist showed 70-90% efficacy over placebo in 1st year and 47-80% efficacy in 2nd year after immunization (219). FluMist promotes virus specific lung TRM and establishes long-term protection compared to inactivated attenuated formulation (220) and was proven safe in a surveillance study (221, 222)."

• "Recently developed mRNA-based vaccines have demonstrated great promise after proven efficacious against severe COVID-19 outcomes, including hospitalization and death. HA (glycoprotein Haemagglutinin)* based mRNA vaccines are in clinical trials, as reviewed in (230) and may have some advantages over conventional inactivated influenza vaccines (231–233). Another approach is to develop a next generation influenza vaccine which triggers heterosubtypic or heterologous immunity (234). Such broad spectrum or non-strain specific vaccine design is feasible by identifying conserved protein regions shared among pre-pandemic and circulating strains via epitope mapping (235, 236). Identification of broadly reactive antigens can be considered as a reverse vaccinology approach which is going to be the most powerful tool for next generation vaccine designing (235). Newborns are particularly at increased risk of severe disease following influenza infection since they may be unable to mount an effective immune response to clear infection. However, a more in-depth understanding of protective responses generated during natural influenza infection can guide development of vaccines which illicit broader responses with limited reactogenicity in these vulnerable populations (237)."

*editor added text