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DOI: 10.31038/JIPC.2022211

Abstract

The specific immune priming can be either through immunization or hyper-immunization approach. Priming of mammalian animals models initiate primary immune response events leading to effector cells formation. Boost activates immune cell to be memory immune cells that are involved in the secondary immune response events. Immunization protocols based either on prime, homologous prime-boost and/or heterologous prime-boost strategies. This theme is operable both in mammalian laboratory animals and human beings. Murine, lapin and primates immune system functions are similar but not identical to that of human beings. So far concerning vaccine development and manufacture. On transition from mammalian laboratory animal to man, there may be variations in responses and/or in vaccine adverse effects. Homologous prime-boost is being the classical and traditional strategy in the national and international vaccination schedules of vaccine preventable infectious diseases for human welfare. Heterologous prime boost strategies are being less sounded in vaccine care givers and in health professional communities. Day by day current trials all over the world were conducted to uncover the validity of use of heterologous prime-boost in mass vaccination of COVID-19. Workers reached one of three conclusions as; i) it reactivate immunogenicity, reactogenicity and/or efficacy ii-Are of comparable efficacy and iii) Preference advise to apply it for mass vaccination of COVID-19. International authority recommendation in this concern is still not in hand. Though, there were few published human volunteer trails for heterologous COVID-19 vaccine strategies.

Keywords

Animal, Boost, COVID-19, Homologous, Heterologous, Prime, Vaccine

Introduction

From the down of COVID-19 till date, the pandemic is circulating, vaccine developed and emergency licensing obtained for few vaccines and vaccine adverse effects were being currently reported in vaccine all over the world. COVID-19 pan mass vaccinations pose to a number of interesting and fascinating topics among which the theme of heterologous prime-boost validity in combating the burden of the sars-cov-2 infections especially those concerning the newly rising variants [1-3]. The objective of the present opinion was to shed a light on the current experimental Coid-19 vaccine designs and vaccine strategies for the application of heterologous prime-boost theme across the globe.

Prime-Boost Theme

In any immunization protocol or schedule, the first applied vaccine shot is known as prime shot, while the following vaccine shots term as booster or boosting shots. The time period between the prime and boost shots depends onto; nature of the vaccine, nature of the receiving immune system, vaccine dose, rout of the proper administration and cautions of the manufacturer. Booster shot induce; memory B cell, memory T cell and both of the memory cells to produce mediator as that for B the antibodies and that of T the cytokines [4,5].

Mammals and Vaccine Development

Small mammalian laboratory animals are eligible for the vaccine laboratory development phase of a newly invented or known vaccines to determine; safety, identity, immunogenicity and efficacy. Efficacy in this case measured from live vaccine challenge model through calculation of morbidity and mortality rate among vaccinated and non-vaccinated test animals. Large primate animals can serve for the preclinical development of a vaccine but mostly used for clinical development of human fetal pathogen as a doublear similar to man [6,7].

Vaccine Prime-Boost in Mammals

Vaccine prime-boost theme is operable both in mammals and man. When a boost shot is of an identical vaccine nature to the prime shot. The schedule is known as homologous prime boost. While when the boosting vaccine shot is for the same pathogen but using different vaccine design and/or different strategies the protocol is termed heterologous prime-boost [5-8].

Mammals-Human Immune Simlulatin

Mammalian immune system is rather similar but not identical to the human immune system. There were found percentages of genetic relatedness between the human genome and genomics and the genome and genomics for mice, rabbit and chimpanzee [9,10]. Rabbit and chimpanzee are genetically more related to human being than mice in the major aspects of the human immune system. Shnawa [10] report about nine immune models of the lapin immune system that simulate for the human immune system among which the vaccine development models [5,6,10]. Though, on transmission from mammalian immune system models to human immune system, there found differences in the nature of in the immune response, efficacy and in the post vaccination vaccine adverse effects. What so ever the nature of these mammalian immune system differences than that of man they stand as an eligible indispensable developmental tool for human vaccine development due to high genetic and immune simulation percentages.

Prime-Boost Theme and Human Vaccine Preventable Diseases

Almost all of the human licensed vaccination schedules in the national and international vaccine list for vaccine preventable communicable infectious disease are of homologous-prime boost type and it is common notion among vaccine care giver and health professionals. Heterologous prime-boost theme is not sounded among vaccine care givers and health professionals. On limited scale it has been tried in HIV, Deng, Ebola [and now it is being experimentally in practice for COVID-19 vaccination in more than one country all over the world (Table 1) [11-15].

Table 1: Vaccines recommended for children aged 0-6 years as homologous prime boost

Bacterial Vaccines

Viral vaccines

Diphtheria toxoid, tetanus toxoid, acellular pertussis Hepatitis A
Haemophilus influenza type b[Hib] Hepatitis B
Meningococcal Influenza
Pneumococcal Measles, Mumps, rubella, polio inactivate, Rotavirus, Varicella

Source: Adapted from [11]

Heterologous Prime-Boost Time Line

DNA prime-protein boost and/or protein boost DNA boost, vector-protein, protein-vector as well as the mRNA-vector, vector-mRNA vaccine strategies were noticed all-over the timeline of heterologous prime boost vaccine designs both in mammals [16-26] and man [27-34] as depicted in Tables 2 and 3.

Table 2: The timeline of heterologous Prime Boost in small mammals and primate

Date

Vaccine Strategy Vaccine immunity

Reference

1991 Priming with live recombinant virus, boost with subunit recombinant protein More effective than either vaccines. It is considered as key principle of heterologous prime boost 16
1991 Prime with recombinant vaccine virus boosted by multiple time with mixture of HIV protein or synthetic peptide Increase in HIV specific antibodies 17
1992 First trail for Heterologous prime boost in nonhuman primates Increase In HIV specific antibody, promising and promote HIV vaccine development 18
1999 DNA-viral vector based in nonhuman primates Good protection. Good inducer to T cell mediated immunity 19
2005-2006 DNA prime-recombinant protein boost with primary HIV Env antigen in nonhuman primates Increase in HIV specific antibodies 20,21,22
2006 DNA prime-protein boost in nonhuman primates Proved effective vaccine strategy, provide active sterilizing immune protection 23
2008

2021

DNA prime-protein boost

Heterologous prime-boost COVID-19 vaccine strategy in nonhuman primate

High frequency responders, HIV specific Antibodies, functional T cell immune responses

Increase in antibody titres

Balanced Th1/TH2 cells

More CD8+ T cells response

24-26

Table 3: The timeline of heterologous prime boost vaccination strategy in human being

Date

Vaccine strategy Vaccine immunity

References

1988 Recombinant vaccine virus HIV coding gene an boosted by recombinant envelope protein First human done by the author himself by inoculating this vaccine strategy gave reasonable individual immunity 27
2005 Vector prime-Protein boost HIV vaccine strategy Induce high antibody and high CD* T cells 28
2008 DNA prime-Protein boost HIV vaccine strategy More significant immunity 21
2016-2019 Ebola heterologous prime-boost vaccine strategy 1a,1b clinical trial in healthy human beings 29,30,31,32
2021 Astrazinicka prime-Pfizer boost COVID-19 heterologous prime boost in human volunteers Significant rise in antibody titre and T cell reactivity 33
2022 Hetero and homologous COVID-19 vaccine strategies for modrena J&J,Pfizer using 458 participant Increase of 6to 73 fold in hetero and 4 to 20 folds rise in neutralizing antibodies and durable T cell mediated immunity 34

Heterologous Prime Boost Strategies and COVID-19 Vaccination

Lessons derived from mass vaccination of COVID-19, showed that the nature of the emergency licensed vaccines and vaccine strategies are of homologous prime-boost nature. Currently, there were reports in more than area across the globe showed that they were tempting heterologous prime boost strategies at an experimental levels. They reached to one of the following conclusions; i) heterologous yield more reactogenicity, more immunogenicity and efficacy than the homologous, ii) homologous and heterologous were of comparable vaccine efficacy and iii) Cautious recommendation for mass vaccination. Strategies tempted for heterologous prime boosts were; i) starting prime boost mono-epitopic followed by multi-epitopic ii) multi-epitopic followed by mono-epitopic vaccines using variable time periods, Table 4, between the prime and the booster shots. Till date no evident international health authority recommend frankly heterologous prime-boost theme in mass vaccination of human against COVID-19 [12,13,34,35].

Table 4: Heterologous, homologous prime –boost versus single vaccine dose in human beings

Priming Nature

Vaccine design and strategy Response nature

References

Prime Astrazinicka Efficacy up to 76% in day 22 to the day 90 post to single vaccine shot 34
Homologous Prime-boost Pfizer-Pfizer, Astrazinicks-Astrazinka Appreciable neutralizing ab rising and CD8+ T cells 35
Heterologous prime-boost Mix Watch of the above makes Higher Ab titre 73 fold High CD8+ T cells 35

Immune Features of Hetrologous Prime Boost both in Mammal and Man

The immune feature of vaccinated small mammals and non-human primate [36,37] as well as that for human beings [35,38,39] are depicted in Table 5. The similarity appeared to be evident in both of the cases.

Table 5: The immune features of heterologous prime boost vaccine strategies in mammal and man

Recipient Immune System

Immune features

References

Mammals; Mice And nonhuman primates i) Make use of existing vaccine candidates

ii) Produce high long term antibody titres especially the neutralizing antibody

iii) Robust germinal center responses

iv) Long term T cell responses

Balanced TH1/TH2 responses

v) High memory CD8+ cells

vi) Immunogenic and effective

vii) Improve TH1 biased T cell responses

viii) Safe, fast and economic

36

37

Human i) Safe, effective. high systemic reactogenicity

ii) Lend profile flexibility for future vaccines

38
Human iii) Increase in the levels of neutralizing antibodies

iv) Provide better protection

v) Combine the best characteristic of each vaccine to enhance the immune system

vi) Advisable to be used in shortage, emergency, low and middle income countries

vii) Heterologous give 6-73 fold rise in neutralizing ab as compared to 4-20 folds in homologous

35,39

Conclusions

Prime and homologous prime-boost vaccine strategies were classically and traditionally known among vaccine care giver and health profession involved in the vaccine community. Heterologous prime-boost, seems to be not known among vaccine workers before 1988. From 1988 onwards to 2022 the scientific community became gradually familiar with the heterologous prime-boost both in; mammals and man. Few current phase I/II human trail using mix and match vaccine strategies for COVID-19, with cautious recommendation for use in low and middle income countries. Though till now international vaccine authority recommendation for mass vaccine implementation concerning heterologous prime boost COVID-19 vaccine strategies is not in hand. Hopes in the coming couple of months or a year, the international vaccine authority be in a position able to license any of experimental and/or the field trail proved heterologous prime boost COVID-19 vaccine strategies.

References

  1. Shnawa IMS (2020) The covid-19 vaccine race, vaccine immunity and vaccine herd immunity. Clin Med Invest 5: 1-4.
  2. Shnawa IMS (2021) Immunity to Sars-cov-2 Infections. Book Publishing International. Science Domain International. India-UK.
  3. Shnawa IMS, ALFatlawi RH, Neamah AH, Abed AS (2021) Determination role of some biomarkers tests for severe Sars-cov-2 infection. Mat. Today; Proceedings, doi.10.1076. matpr. 2021-08.223.
  4. AL-Shaery MAN, Shnawa IMS (1998) The immune-adjuvant effect of sunflower oil. Vet Med J Giza 37: 291-298.
  5. Shnawa IMS (2021) Lapin immune features of experimental Escherichia coli-Pseudomonas aeruginosa combined bacterin. J Hunan Uni Natural Science 48: 388-399.
  6. Shnawa IMS (2019) Vaccine Technology At Glance. Boffin Access UK 36-48.
  7. Shnawa IMS (2016) Vaccinology At Glance. Lap Lambert Academic Publication, Germany 11-29.
  8. Shnawa IMS (2021) Animal contributions to immunology. J Hunan Uni Nat Sci 48: 330-335.
  9. Shnawa IMS (2013) Lapin Mucosal Immunology Lap Lambert Academic Publication, Germany 5-17.
  10. Shnawa IMS (2021) Lapin-Human Immune Simulation Models. Book Publishing International. Science Domain International India-UK.29-52.
  11. Levinson W, Chin-Hong P, Joyce EA, Nussbaum J, Schwartz B (2018) Review of Medical Microbiology and Immunology15th ed, McGraw-Hill/Lange, New York 273.
  12. Lu S (2009) Heterologous Prime-Boost vasccination. Curr Opin Immunol 21: 245-251.
  13. Siddiqui A, Adnan A, Abbas M, Taseen S, Ochani S, Essar MY (2022) Revival of heterologous prime-boost :An outlook from the history of outbreaks. Hlth Sci Rep 5: 531. [crossref]
  14. George JA, Eo SK (2011) Distinct humoral and cellular induced by alternative prime boost vaccination using plasmid DNA and live viral vector vaccination expression of E protein of Denge virus type2. Immune Network 11: 268-280. [crossref]
  15. Brown SA, Surman SL, Sealy R (2010) Heterologous Prime-boost HIV vaccination regimen in pre-clinical trials. Viruses 2: 435-467. [crossref]
  16. Hu SL, Kalniecki J, Sirdhar P, Travis BM (1991) Neutralizing antibodies against HIV-1BRU and SF2 isolates generated in mice immunized with recombinant virus expressing HIV-1BRU envelope glycoproteins and boosted with homologous gp 160 AIDS Res, Hum. Reteroviruses 7: 615-620. [crossref]
  17. Girard M, Kieny MP, Barre-Sinouss F, Nara P, Kolbe H, et al. (1991) Immunization of chimpanzee confer protection against challenge with human immune deficiency virus. Proc Nat Acad Sci USA 88: 542-546. [crossref]
  18. Hu SL, Abrams K, Barber GN, Moran P, Zarling JM, et al. (1992) Protection of macaques against SIV infection by subunit vaccine of SIV envelope glycoprotein 160. Science 255: 456-459. [crossref]
  19. Hank T, Samuel RV, Blanchard TJ, Neumann VC, Allen TM, et al. (1999) Effective induction of simian immune deficiency virus specific cytotoxic T lymphocytes in macaques by using multiepitopic gene and DNA prime-modified vaccine virus Ankara boost vaccine regimen. J Virol 73: 7524-7532. [crossref]
  20. Beddows S, Schulke N, Kirschner M, Barnes K, Franti M, et al. (2005) Evaluating immunogenicity of disulfide stabilized, cleaved tri-meric form of envelope glycoprotein complex of human immunodeficiency virus 1. J virol 79: 8812-8827. [crossref]
  21. Wang S, Arthus J, Lawrence JM, Ryk DV, Innocent M, et al. (2005) Enhanced immunogenicity of gp120 protein when combined with recombinant DNA priming to generate antibodies that neutralize the JR-FL priming isolate of HIV-I. Virol 19: 7933-79337. [crossref]
  22. Wang S, Pal R, Mascola JR, Chou THW, Innocent M, et al. (2006) Polyvalent HIVI envelope vaccine formulations delivered by the DNA priming HIV-I isolate subtypes A, B, C, D & E. Virol 350: 34-47. [crossref]
  23. Pal R, Kalyanaraman VS, Nair BC, Whitney S, Keen T, et al. (2006) Immunization of rhesus macaques with polyvalent DNA prime-protein boost HIV-I vaccine elicit protective antibody response against siamian human immune deficiency virus of R5 phenotype Virology 348: 341-353. [crossref]
  24. Wang S, Kennedy JS, West K, et al. (2008) Cross-subtype antibody and cellular immune responses induced by polyvalent DNA prime-protein boost HIV-I vaccine in healthy volunteers. Vaccine 26: 1098-1110.
  25. Bansal A, Jackson B, West K, Wang S, Lu S, et al. (2008) Multi-functional T cell characteristics induced by polyvalent DNA prime-protein boost human immune deficiency virus type I vaccine regimen given to healthy adults are dependent on the rout and dose administered. Virol 82: 6458-6469. [crossref]
  26. Liu J, Xu K, Xing M, et al. (2021) Heterologous prime boost immunization with chimpanzee adenoid vector elicit potent protective immunity against sars-cov-2 infection. Cell Discovery 7: 123.
  27. Zagury D, Bernard J, Cheyneir R, Desportes I, Leonard R, et al (1988) A group specific anamestic immune reaction against HIV-I induced by a candidate vaccine against AIDS. Nature 332: 728-731. [crossref]
  28. Nitonyaphan S, Pitisuttithum P, Karmasuta C, Eamsila C, Souza MD, et al. (2004) Safety and immunogenicity of an HIV subtype B and E prime-boost combination in HIV negative Thia adults. J Infect Dis 190: 702-706. [crossref]
  29. Wang QM, Sun SH, Hu ZL, Yin M, Xiao CJ, et al. (2004) Improved immunogenicity of tuberculosis DNA vaccine by DNA priming and protein boosting. Vaccine 22: 3622-3527. [crossref]
  30. University of Oxford (2016) A phase I a clinical trial to assess the safety and immunogenicity of MVA-EBOZ alone and a heterologous prime-boost with ChAd3-EBOZ in healthy UK volunteers. Clinical trial.gov.2016.Report Number NCT0Z451891.
  31. University of Oxford (2019) A Phase I b safety and immunogenicity. Clinical trial of heterologous prime boost immunization with MBOZ an MVA-EBIZ in healthy Senegalese adults aged 18-50 years. Report NumberNCT02485912.
  32. Venkatraman N, Ndiaye BP, Bowyer G, Wade D, Sridhar S, et al. (2019) safety, and immunogenicity of a heterologous prime boost EBOLA virus vaccine regimen in healthy adults in UK and Senegal. J Infect Dis 219: 1187-1197. [crossref]
  33. Gro BR, Zanoni M, Seid IA et al. (2021) heterologous chldoxin cov-19 andBNT162bz prime boost vaccination elicit potent neutralizing antibodies and T cell reactions. mdRxiv 21257971.
  34. Voyasey M, Clemens SAC, Madhi SA, et al. (2021) Sigle dose administration and the influence of the timing of the booster dose on the immunogenicity and efficacy of Chdoxin covid19 (AZD1222) vaccine a pooled analysis. Lancet 397: 881.
  35. Atmar RL, Lyke KE, Deming ME, et al. (2022) Homologous and heterologous covid-19 booster vaccination. New Eng J Med 386: 11.
  36. Lu S, Wang S, Grimes-Serrani JM (2008) Current progress of DNA vaccine studies in human. Expert Rev Vaccine 7: 175-191. [crossref]
  37. He Q, Mao Q, An C, Zhang J, Gao F, et al. (2021) Heterologous prime boost; breaking the protective immune response bottole neck of covid-19 vaccine candidate. Emerg Microbe Infect 10: 629-637. [crossref].
  38. Sapktota B, Saud B, Shretha R, Fahad DA, Sah R, et al.(2022). Heterologous prime boost strategies covid-219 vaccine. Trav.Med [crossref]
  39. Zhang R, Liu D, Leung KY, Fan Y, Lu L, et al. (2022) Immunogenicity of a heterologous prime-boost covi-19 vaccination with mRNA and inactivated vaccines compared with homologous vaccination strategy against sars-cv-2 variants. Vaccine 10: 72. [crossref]

Article Type

Research Article

Publication history

Received: May 03, 2022
Accepted: May 11, 2022
Published: May 18, 2022

Citation

Shnawa IMS (2022) Opinion; Heterologus Prime-Boost as COVID-19 Vaccine Strategies: Towards a Nationwide Implementation. J Int Pers COVID-19 Volume 2(1): 1–4. DOI: 10.31038/JIPC.2022211

Corresponding author

Dr. Ibrahim MS Shnawa
Department of Anesthesia
Hilla University College and Department of Biotechnology College of Biotechnology
University of Qasim
Babylon
Iraq