HJNO Jan/Feb 2021

20 JAN / FEB 2021  I  HEALTHCARE JOURNAL OF NEW ORLEANS COVID-19 VACCINE 2.0 aluminum oxyhydroxide (43), aluminum hydroxide (11), aluminum phosphate (22), and Imject™ Alum (23), which is a mixture of aluminum hydroxide and magnesium hydroxide. Even though there is no spe- cific description regarding the aluminum hydroxide in reported literature (11, 18, 21), it can also be referred to Aluminum oxyhy- droxide (44). However, these studies lacked systematic comparisons with regards to their adjuvanticity and how various alum- based adjuvants differed in their ability to induce neutralizing antibodies. It is worth noting that inactivated SARS- CoV or S protein-based vaccines are as- sociated with Th2-type immunopathology, which is characterized by an increase in eosinophils and inflammatory infiltrates (14, 30, 37, 45). Moreover, the addition of alum adjuvant exacerbated the immu- nopathologic reactions (14, 45). In alum- adjuvanted SARS-CoV double-inactivated vaccine (DIV), there was a skew in the N or S protein-specific antibodies toward IgG1, when compared with the more bal- anced antibody production in the nonad- juvanted DIV vaccine (14). These observa- tions raise significant concerns regarding the safety of adjuvanted coronavirus vac- cines. On the other hand, it has been shown that alum can reduce immunopathology in SARS-CoV vaccines containing either a double-inactivated virus or S protein (11). Furthermore, in a recent study, a purified inactivated SARS-CoV-2 vaccine (PiCo- Vacc) adjuvanted with aluminum hydrox- ide conferred complete protection in non- human primates (rhesus macaques) with potent humoral responses but without lung immunopathology (15). This finding raises the question of the mechanism of eosino- philic immunopathology. While commonly thought of as the product of Th2 respons- es, recent studies have indicated that tis- sue eosinophilia can also be controlled by Th17 responses (46). Thus, the proper selection of CoV antigens and adjuvants that can shift host responses away from a Th17-bias appears to be critical. In addi- tion, other studies have demonstrated that the Th2 immunopathology may be associ- ated with SARS N or S protein that results in enhanced eosinophilic immunopathol- ogy (11, 37, 47). However, more studies are required, as the preliminary data is limited. Additionally, the Th-2–biased immune re- sponses may raise the concern on vaccine- rently in the pipeline from Moderna and Bi- oNTech/Pfizer seem new to the public, they have been extensively studied and advanced in animal models for more than 20 years. Through these scientific endeavors, vast im- provements were made in terms of their sta- bility and immunogenicity (ability to induce an immune response), which ultimately has led to increased efficacy in humans as we are currently witnessing. Furthermore, the mRNA technology used by Moderna and BioNTech/ Pfizer were already being evaluated in human clinical trials for vaccines against other infec- tious diseases, such as Zika and Cytomega- lovirus, which is one of the reasons why the mRNA platform could be adapted so quickly to address the urgent need for a COVID-19 vaccine. Do you think this first generation of vaccines will halt the pandemic? Why or why not? JAMES MCLACHLAN: No, but we be- lieve it will certainly slow the pandemic by limiting the greatest loss of life through im- munization of the most exposed population (health care workers) and the most vulnerable (the elderly). A number of issues affect actu- ally halting the pandemic, even with the first generation of vaccines. The first is the role for herd immunity and vaccine uptake. In order to achieve herd immunity, where the unim- munized population is generally protected from infection by being surround by a “herd” of immunized people, the estimates are that at least 65% of the population must be im- munized. This estimate depends on the level of transmissibility of the virus and its mode of transmission, although the herd percentage required may actually be higher than this. A recent poll put the percent of people in the U.S. willing to get the vaccine at 58%, which is not quite what is needed for herd immunity. This is one reason that the first generation of vaccines may not halt the pandemic – the up- take by the population may just not be high enough. The second reason is, while we are learning vast amounts rapidly about this vi- rus, we still do not completely understand it. It may be that while a good vaccine, as the first-generation vaccines appear to be, can prevent severe disease in people who are ex- posed to the virus, these vaccines may not be able to prevent transmission of the virus from vaccinated people to unvaccinated people. A similar phenomenon exists with the child- hood vaccine for whooping cough (Called DTaP or TDaP). While the whooping cough vaccine can prevent disease in immunized people, it often doesn’t prevent transmission of the bacteria that causes whooping cough from immunized people to unimmunized people. It is possible this will occur with the virus that causes COVID-19 and the first gen- eration of vaccines as well. This leads to the final reason these vaccines mat not halt the pandemic, and that it is likely important for the most potent vaccines to induce mucosal immunity. Every part of the body can display an immune response, but most vaccine-me- diated immune responses are concentrated in the blood or in the lymphatic system. These types of immune response are often perfectly adequate for preventing and even eliminating some infectious diseases. Others require that the mucosa, the so called “ports of entry” for the disease, be specifically pro- tected by the immune response. In the ex- ample of COVID-19, the virus infects via the lungs or the respiratory mucosa. Inducing an immune response directly in these tissues would likely greatly enhance the efficacy of a vaccine against COVID-19 and should be the goal of second-generation vaccines and beyond. Testing/clinical trial protocols were supposably established for a reason