COVID-19: Mechanisms of Vaccination and Immunity

Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

Download Full-text

Vaccines against Coronavirus Disease: Target Proteins, Immune Responses, and Status of Ongoing Clinical Trials

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.14.4.03 ◽

2020 ◽

Vol 14 (4) ◽

pp. 2253-2263

Author(s):

Rike Syahniar ◽

Maria Berlina Purba ◽

Heri Setiyo Bekti ◽

Mardhia Mardhia

Keyword(s):

Clinical Trials ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Host Cells ◽

Rapid Transmission ◽

Adequate Dosage ◽

Immunogenic Response ◽

Selection Of

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 26 million individuals and caused 871,166 deaths globally. Various countries are racing against time to find a vaccine for controlling the rapid transmission of infection. The selection of antigen targets to trigger an immune response is crucial for vaccine development strategies. The receptor binding domain of the subunit of spike 1 protein is considered a promising vaccine candidate because of its ability to prevent attachment and infection of host cells by stimulating neutralizing antibodies. The vaccine is expected to mount a sufficient immunogenic response to eliminate the virus and store antigenic information in memory cells for long-term protection. Here, we review the ongoing clinical trials for COVID-19 vaccines and discuss the immune responses in patients administered an adequate dosage to prevent COVID-19.

Download Full-text

Inflammatory Neuropsychiatric Disorders and COVID-19 Neuroinflammation

Acta Neuropsychiatrica ◽

10.1017/neu.2021.13 ◽

2021 ◽

pp. 1-55

Author(s):

Siu Wa Tang ◽

Daiga Helmeste ◽

Brian Leonard

Keyword(s):

Immune Responses ◽

Clinical Management ◽

Neuronal Damage ◽

Treatment Resistance ◽

Neuropsychiatric Disorders ◽

Acute Stage ◽

Management Approach ◽

Neuropsychiatric Diseases ◽

Anti Inflammatory

Abstract Neuropsychiatric sequalae to COVID-19 infection are beginning to emerge, like previous Spanish influenza and SARS episodes. Streptococcal infection in pediatric patients causing OCD (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, wide-spread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long term specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favorable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease modifying therapies are increasingly being applied to neuropsychiatric diseases characterized by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.

Download Full-text

Chapter 14: Prevention: vaccines and immunoglobulins

Tick-borne encephalitis - The Book ◽

10.33442/26613980_14-4 ◽

2021 ◽

Author(s):

Eva-Maria Pöllabauer ◽

Herwig Kollaritsch

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Western Europe ◽

Surrogate Marker ◽

Booster Vaccination ◽

Post Exposure Prophylaxis ◽

Pediatric Formulation ◽

The One ◽

Exposure Prophylaxis

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao. All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

Download Full-text

Rectal Acquisition of Simian Immunodeficiency Virus (SIV) SIVmac239 Infection despite Vaccine-Induced Immune Responses against the Entire SIV Proteome

Journal of Virology ◽

10.1128/jvi.00979-20 ◽

2020 ◽

Vol 94 (24) ◽

Author(s):

Mauricio A. Martins ◽

Lucas Gonzalez-Nieto ◽

Michael J. Ricciardi ◽

Varian K. Bailey ◽

Christine M. Dang ◽

...

Keyword(s):

T Cells ◽

Virus Infection ◽

Immune Responses ◽

Simian Immunodeficiency Virus ◽

Vaccine Efficacy ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Hiv Vaccine ◽

Partial Control ◽

Immunodeficiency Virus

ABSTRACT Given the complex biology of human immunodeficiency virus (HIV) and its remarkable capacity to evade host immune responses, HIV vaccine efficacy may benefit from the induction of both humoral and cellular immune responses of maximal breadth, potency, and longevity. Guided by this rationale, we set out to develop an immunization protocol aimed at maximizing the induction of anti-Envelope (anti-Env) antibodies and CD8+ T cells targeting non-Env epitopes in rhesus macaques (RMs). Our approach was to deliver the entire simian immunodeficiency virus (SIV) proteome by serial vaccinations. To that end, 12 RMs were vaccinated over 81 weeks with DNA, modified vaccinia Ankara (MVA), vesicular stomatitis virus (VSV), adenovirus type 5 (Ad5), rhesus monkey rhadinovirus (RRV), and DNA again. Both the RRV and the final DNA boosters delivered a near-full-length SIVmac239 genome capable of assembling noninfectious SIV particles and inducing T-cell responses against all nine SIV proteins. Compared to previous SIV vaccine trials, the present DNA-MVA-VSV-Ad5-RRV-DNA regimen resulted in comparable levels of Env-binding antibodies and SIV-specific CD8+ T-cells. Interestingly, one vaccinee developed low titers of neutralizing antibodies (NAbs) against SIVmac239, a tier 3 virus. Following repeated intrarectal marginal-dose challenges with SIVmac239, vaccinees were not protected from SIV acquisition but manifested partial control of viremia. Strikingly, the animal with the low-titer vaccine-induced anti-SIVmac239 NAb response acquired infection after the first SIVmac239 exposure. Collectively, these results highlight the difficulties in eliciting protective immunity against immunodeficiency virus infection. IMPORTANCE Our results are relevant to HIV vaccine development efforts because they suggest that increasing the number of booster immunizations or delivering additional viral antigens may not necessarily improve vaccine efficacy against immunodeficiency virus infection.

Download Full-text

SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity

10.1101/2021.05.09.443331 ◽

2021 ◽

Author(s):

M. Gordon Joyce ◽

Kayvon Modjarrad

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Development ◽

Design Strategies ◽

Virus Challenge ◽

High Magnitude ◽

Antigenic Properties ◽

Blocking Activity ◽

Antibody Titers ◽

Engineered Nanoparticle

The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle (RFN) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18-hACE2 transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development.

Download Full-text

Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

Vaccines ◽

10.3390/vaccines9080852 ◽

2021 ◽

Vol 9 (8) ◽

pp. 852

Author(s):

Khalid A. Alluhaybi ◽

Rahaf H. Alharbi ◽

Rowa Y. Alhabbab ◽

Najwa D. Aljehani ◽

Sawsan S. Alamri ◽

...

Keyword(s):

Immune Responses ◽

Dna Vaccine ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Cell Responses ◽

Cellular Immune Responses ◽

Specific Igg ◽

Cellular Immune ◽

Different Doses

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

Download Full-text

Recombinant Herpesvirus Vectors: Durable Immune Responses and

Journal of Virology ◽

10.1128/jvi.00330-21 ◽

2021 ◽

Author(s):

Isabelle M. Castro ◽

Michael J. Ricciardi ◽

Lucas Gonzalez-Nieto ◽

Eva G. Rakasz ◽

Jeffrey D. Lifson ◽

...

Keyword(s):

Immune Responses ◽

Simian Immunodeficiency Virus ◽

Vaccine Development ◽

Rhesus Macaques ◽

Antigen Expression ◽

Challenge Virus ◽

Immunodeficiency Virus ◽

Herpesvirus Vector ◽

Gamma Herpesvirus

A prophylactic vaccine that confers durable protection against human immunodeficiency virus (HIV) would provide a valuable tool to prevent new HIV/AIDS cases. As herpesviruses establish lifelong infections that remain largely subclinical, the use of persistent herpesvirus vectors to deliver HIV antigens may facilitate the induction of long-term anti-HIV immunity. We previously developed recombinant (r) forms of the gamma-herpesvirus rhesus monkey rhadinovirus (rRRV) expressing a replication-incompetent, near-full-length simian immunodeficiency virus (SIVnfl) genome. We recently showed that 8/16 rhesus macaques (RMs) vaccinated with a rDNA/rRRV-SIVnfl regimen were significantly protected against intrarectal (IR) challenge with SIVmac239. Here we investigated the longevity of this vaccine-mediated protection. Despite receiving no additional booster immunizations, the protected rDNA/rRRV-SIVnfl vaccinees maintained detectable cellular and humoral anti-SIV immune responses for more than 1.5 years after the rRRV boost. To assess if these responses were still protective, the rDNA/rRRV-SIVnfl vaccinees were subjected to a second round of marginal-dose IR SIVmac239 challenges, with eight SIV-naïve RMs serving as concurrent controls. After three SIV exposures, 8/8 control animals became infected, compared to 3/8 vaccinees. This difference in SIV acquisition was statistically significant (P = 0.0035). The three vaccinated monkeys that became infected exhibited significantly lower viral loads than those in unvaccinated controls. Collectively, these data illustrate the ability of rDNA/rRRV-SIVnfl vaccination to provide long-term immunity against stringent mucosal challenges with SIVmac239. Future work is needed to identify the critical components of this vaccine-mediated protection and the extent to which it can tolerate sequence mismatches in the challenge virus. IMPORTANCE We report on the long-term follow-up of a group of rhesus macaques (RMs) that received an AIDS vaccine regimen and were subsequently protected against rectal acquisition of simian immunodeficiency virus (SIV) infection. The vaccination regimen employed included a live recombinant herpesvirus vector that establishes persistent infection in RMs. Consistent with the recurrent SIV antigen expression afforded by this herpesvirus vector, vaccinees maintained detectable SIV-specific immune responses for more than 1.5 years after the last vaccination. Importantly, these vaccinated RMs were significantly protected against a second round of rectal SIV exposures performed one year after the first SIV challenge phase. These results are relevant for HIV vaccine development because they show the potential of herpesvirus-based vectors to maintain functional antiretroviral immunity without the need for repeated boosting.

Download Full-text

HIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions

Journal of Immunology Research ◽

10.1155/2015/560347 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Muni Rubens ◽

Venkataraghavan Ramamoorthy ◽

Anshul Saxena ◽

Nancy Shehadeh ◽

Sandeep Appunni

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Recombinant Dna ◽

Vaccine Development ◽

Hiv Vaccine ◽

Future Directions ◽

Treatment Protocols ◽

Mortality And Morbidity ◽

Host Immune Responses ◽

Hiv Aids

HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines.

Download Full-text

Chapter 14: Prevention – Vaccines + Immunoglobulins

Tick-borne encephalitis - The Book ◽

10.33442/978-981-14-0914-1_14 ◽

2019 ◽

Cited By ~ 1

Author(s):

Eva-Maria Pöllabauer ◽

Herwig Kollaritsch

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Western Europe ◽

Surrogate Marker ◽

Booster Vaccination ◽

Post Exposure Prophylaxis ◽

Pediatric Formulation ◽

The One ◽

Exposure Prophylaxis

• Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. • The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao • All TBE vaccines except the one from China have similar but not identical immunization sched-ules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir a rapid immunization schedules is also licensed. The Chinese vaccine is giv-en with 2 primary doses 2 weeks apart followed by annual boosters. • All vaccines induce significant immune responses. In the absence of a formal correlate of pro-tection, the presence of neutralizing antibodies is used as a surrogate marker for protection. • Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. • An effectiveness of approximately 99% (years 2000–2006) and 98,7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccina-tion uptake. • Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. • Both - FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

Download Full-text

Integrating fish models in tuberculosis vaccine development

Disease Models & Mechanisms ◽

10.1242/dmm.045716 ◽

2020 ◽

Vol 13 (8) ◽

pp. dmm045716

Author(s):

Anni K. Saralahti ◽

Meri I. E. Uusi-Mäkelä ◽

Mirja T. Niskanen ◽

Mika Rämet

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Bacillus Calmette Guerin ◽

Antibiotic Resistant ◽

Vaccine Candidates ◽

Preclinical Evaluation ◽

Vaccination Strategies ◽

Resistant Strains ◽

New Vaccines

ABSTRACTTuberculosis is a chronic infection by Mycobacterium tuberculosis that results in over 1.5 million deaths worldwide each year. Currently, there is only one vaccine against tuberculosis, the Bacillus Calmette–Guérin (BCG) vaccine. Despite widespread vaccination programmes, over 10 million new M. tuberculosis infections are diagnosed yearly, with almost half a million cases caused by antibiotic-resistant strains. Novel vaccination strategies concentrate mainly on replacing BCG or boosting its efficacy and depend on animal models that accurately recapitulate the human disease. However, efforts to produce new vaccines against an M. tuberculosis infection have encountered several challenges, including the complexity of M. tuberculosis pathogenesis and limited knowledge of the protective immune responses. The preclinical evaluation of novel tuberculosis vaccine candidates is also hampered by the lack of an appropriate animal model that could accurately predict the protective effect of vaccines in humans. Here, we review the role of zebrafish (Danio rerio) and other fish models in the development of novel vaccines against tuberculosis and discuss how these models complement the more traditional mammalian models of tuberculosis.

Download Full-text