>> Importantly cannot determinecausality of a diverse event. Next. Next slide. As of October 10, 2021, there were 4,990reports VAERS following dose two Janssen or dose three of mRNA COVID-19 vaccine. The median age was 64 years, and63% of reports were from women. Next slide. Race or ethnicity was unknown or incompletefor 49% of reports and 39% were from persons who identified as white/non-Hispanic. Next slide. Overall, 94% of the 4,990 VAERS reportsfollowing dose two of Janssen or dose three of mRNA COVID-19 vaccination were nonserious.This varies slightly by vaccine manufacturerbut is similar to what we’ve observed for COVID-19 vaccines overalland other vaccines in general. Next slide. Among serious reports, the mostcommon adverse event reported to VAERS was extra dose administered. Among nonserious reports, the mostcommon adverse event was interchange of vaccine products. This may mean that the additiondose was given in error or given outside of recommendations at the time. Per federal law, serious reportsinclude reports of hospitalization, prolongation of existing hospitalization, lifethreatening conditions, permanent disability, congenital deformity or birth defect, or death. Also, please note that these adverseevents are not mutually exclusive, and a report may includemore than one adverse event. Next. Among the millions of persons who havereported a third dose of mRNA or a second dose of Janssen COVID-19 vaccine, therewere 30 reports of death to VAERS. There were no reports of deathfollowing dose two of Janssen. The median age was 79 years. Median time elapsed from thirddose to death was two days.A CDC physician received the availabledocumentation, including death certificate, to determine a preliminaryimpression of cause of death. We were unable to determine causeof death due to insufficient data. Next. VAERS is also monitoring reports ofadverse events following co-administration of COVID-19 vaccine and other vaccines. Most reports to VAERS does notspecify the vaccine type administered with the COVID-19 vaccine. Influenza and Zoster vaccine were amongthe most common vaccine types specified. The most commonly reported adverse eventsincluded extra dose or expired products, systemic symptoms, or adverseevents unique to Zoster. VAERS will continue to monitor adverseevents following co-administration. Next slide. Now, I will review data from v-safe. v-safe is a voluntary, smartphone-basedsafety surveillance system. v-safe allows existing participants to reportreceiving an additional dose of COVID-19 vaccine and new participants to enter informationabout all doses of COVID-19 vaccine received and complete health surveyson the most recent dose. v-safe health surveys are sent duringthe week following each dose of vaccine and include questions about local injectionsite and systemic reactions and health impacts, including inability to perform normal,daily activities, inability to work or attend school, and receipt of medical care.Additional health surveys are sent weeklythrough six-week factor vaccination and at three, six, and 12months after vaccination. Next slide. The key strengths of v-safe are that it’seasy to use, includes active outreach to participants, and collects longitudinal data. The key limitations include that enrollment inv-safe is voluntary and requires a smartphone, and importantly cannot determinecausality of adverse events. Next slide. As of October 10, 2021, over 274,000 v-safeparticipants had reported an additional dose of COVID-19 vaccine. Sixty-two percent of participants were female. Thirty-nine percent were age 65 to 74 years. Ninety percent of participants identifiedas non-Hispanic, and 84% as white. Next slide. This table shows the patterns of vaccination for v-safe participants whoreported an additional dose. The column shows primary seriesreceived and rows show additional dose. Bolded in blue are those whoreceived the same manufacturer for primary series and additional dose. Over 98% of participants reported athird dose from the same manufacturer as their primary mRNA vaccine series.Most participants report threedoses of Pfizer BioNTech vaccine. Next slide. This figure shows the top tensolicited reactions reported at least once during days zerothrough seven after dose three of Moderna or Pfizer BioNTech vaccine. Moderna shown in blue andPfizer BioNTech in orange. Pain, fatigue, myalgia, and headache were amongthe most frequently reported solicited reactions for both vaccines. Next slide. This figure shows reactions in health impactevents reported at least once during day zero to seven after Pfizer BioNTechvaccination by dose. The odds of reporting andevent following dose two and three were compared using a multivariable,generalized estimating equations model that accounted for the correlationbetween participants and adjusted for demographic variables. P values less than 0.05 were consideredto be statistically significant and are indicated here by an asterisk. Injection site reactions, systemic reactions,and health impacts including inability to perform daily activities and inability to work were all less frequentfollowing dose three than dose two. Next slide. This figure shows reactions in health impactevents reported at least once during day zero to seven after Moderna vaccination by dose.Injection site reactions were morefrequently reported following dose three of Moderna vaccine than dose two. While systemic reactions and healthimpacts, including inability to work, were less frequent followingdose three than dose two. While these differences were statisticallysignificant, the magnitude was small. Next slide. v-safe is also monitoring reactionsreported following co-administration of COVID-19 vaccine and other vaccines. Over 65,000 v-safe participantsreported receiving another vaccine at the same time as their COVID-19 vaccine. Most were aged 18 to 75 years. Nearly 90% of co-administered vaccines wasgiven with dose three of COVID-19 vaccine. v-safe will continue to monitor reactionsreported following co-administration.Next slide. These data are subject toa number of limitations. First, both VAERS and v-safe are volunteersystems and are likely not representative of the vaccinated U.S. population. Second, additional dose recommendationsinclude immunocompromised persons who completed a primary seriesof mRNA COVID-19 vaccine. However, v-safe does not includespecific information about immune status. Additional dose recipientslikely included immunocompromised and non-immunocompromised persons. And immunocompromised personsmight have a different reactogenicity than immunocompetent persons. Third, approximately half of mRNA third dosesare among persons aged 65 years and older who might have different reactogenicitythan persons in different age groups. Fourth, at this time, data are limitedto determine patterns of adverse events after receipt of second dose from Janssen or from the manufacturerdifferent from the primary series. This also limited our ability toidentify the rare adverse events. Finally, complete medical review ofdeaths following vaccinations reported to VAERS is dependent on availability of medicalrecords, death certificates, and autopsy reports which may be delayed or not available. Next slide. To summarize, we did not observe anyunexpected patterns of adverse events. However, the data are limited at thispoint to identify rare adverse events.Nearly all reports of VAERS were nonserious. Most commonly reported werevaccination errors and systemic symptoms. Most v-safe participants reported aprimary mRNA vaccine series followed by dose three from the same manufacturer. For Pfizer BioNTech, local and systemicreactions were reported less frequently following dose three than dose two. For Moderna, local reactions werereported slightly more frequently, and systemic reactions slightly lessfrequently following dose three than dose two. Next slide. VAERS and v-safe will continue to monitor safetyof additional doses of COVID-19 vaccinations. Additionally, Vaccine Safety Datalinkwill incorporate additional doses into its ongoing safety monitoring. And CISA will be available to consulton clinically complex adverse events. We will update ACIP as additionaldata become available. Next slide. The Vaccine Safety Team is incrediblygrateful to all of the v-safe participants and to those who complete VAERS reports.We’d like to encourage everyone to reportadverse events that occur following vaccination to VAERS, even if you’re unsurevaccination caused the event. Also, please enroll yourself in v-safe. If you’re a healthcare provider,encourage your patients to enroll. If you’re a parent, enroll your childrenand complete surveys on their behalf. The data collected through thesesystems are extremely valuable. Please get involved and encourageothers to do so as well. Next slide. Finally, thank you to the many peoplewho contributed to these analyses. This concludes my presentation. >> Good afternoon, everybody. This is Kathleen Dooling, and I willbe reviewing the recommendations for COVID-19 vaccine booster doses and highlighting the evidence that ACIPexamined to inform these recommendations. Next slide, please. I’d like to start the presentationwith the bottom line. The two recommendations madeby ACIP last Thursday. The first was that the following recipients of mRNA COVID-19 vaccine primary series shouldreceive a single dose at least six months or more after completion of the primary series. And those are people 65 years and older as wellas people 18 years of age and older who reside in long-term care settings as well aspeople 50 to 64 years old with underlying, certain underlying medical conditions.In addition, the following recipients of mRNA COVID-19 vaccine primary series mayreceive a single booster dose six months or more after completion of the primary seriesbased on their individual risks and benefits. So, those are people 18 to 49 years oldwith certain underlying medical conditions and people 18 to 64 years old at increasedrisk of SARS-CoV-2 exposure and transmission because of their occupationalor institutional setting. Next slide. The second recommendation was that CDCrecommends that people who are 18 years of age and older who received a Janssen COVID-19vaccine should receive a booster at a minimum of two months following the initialreceipt of their Janssen vaccine. Another important aspect of therecommendations are that highlight that any of the authorized COVID-19 vaccine boosterdoses, so that’s Pfizer BioNTech, Moderna, or Janssen, can be used following anyof the primary series vaccinations.The term used for a booster which is different from your primary series is heterologousboosting, also known as mix and match. And now, I’ll go on to share some of the evidence the ACIP usedto inform these recommendations. Next slide. As of October 20, more than 189million people age 12 years of age and older have been fully vaccinatedin the U.S. Approximately 66% of people have been fully vaccinatedwith the Pfizer primary series. Approximately 37% with Modernaprimary series, and approximately 8% with a dose of Janssen COVID-19 vaccine. Next slide. This slide shows the trends inthe number of daily COVID-19 cases in the U.S. Now totaling approximately 45million since the beginning of the pandemic. Currently, during which Delta variant haspredominated, peaked in early September and has been on the decline since then. Next slide. Similarly, the daily trends in the number ofhospitalized COVID-19 cases has been declining in the U.S. over the past several weeks. Next slide. So, this figure is an update from COVID-NETwhich is a hospital-based surveillance system that allows for chart review of COVID cases. The data shown here is for ageadjusted weekly hospitalization rates, stratified by age group fromJanuary through August.Hospitalization rates among fullyvaccinated people are shown in the green, and hospitalization rates in unvaccinatedpeople are shown in the blue line. In July and August, as hospitalization ratesincreased dramatically among the unvaccinated, rates increased only slightlyamong the fully vaccinated. Among the various age groups,hospitalization was nine to 15 times higher amongunvaccinated compared to vaccinated. Next slide. And of course, hospitalization is not theonly debilitating consequence of COVID-19. Long COVID conditions are awide range of new, returning, or ongoing health problems peoplecan experience four or more weeks after being infected with the SARS-CoV-2 virus. Prevalence of post COVID-19 conditions,both among vaccinated and unvaccinated, has been reported to be frombetween 5% and 80% of COVID cases. The prevalence of long COVID among fullyvaccinated persons who develop COVID ranges from reports stating 5% in astudy among UK adults to about 19% in a study of Israeli healthcare workers.And among COVID-19 cases in that same UKstudy, the odds of long COVID were reduced by half among fully vaccinatedpeople compared to unvaccinated. Next slide. So, switching gears, now. I would like to review a summary of vaccineeffectiveness of the primary vaccine series. Waning of mRNA vaccines has been more pronouncedagainst infection shown in this graph in blue than against hospitalization shown here in red. Compared to the pre-Delta period, vaccine effectiveness has generallybeen lower in the Delta period. Next slide. And as demonstrated in this figure ofpublished vaccine effectiveness studies, mostly involving mRNA vaccines, waning against infection has been mostpronounced in July during the Delta period. Nanduri et al. depicted in the light blue in this figure,reported that VE among nursing home residents that was lower than that found in youngeradults, and it did wane over time. Next slide. So, vaccine effectiveness againsthospitalization, on the other hand, has remained fairly constant over calendar time. In this range of studies, all above 80%. Next slide. And VE against hospitalizationswas also constant when analyzed against time since vaccination.As seen here in the red, Janssen vaccineeffectiveness was lower than that assessed, the vaccine effectivenessassessed for mRNA vaccines. Next slide. So, to summarize the protectionafforded by COVID vaccine primary series, more than 189 million people inthe U.S. are fully vaccinated. That’s approximately 57%of the total population. Hospitalization rates are nine to15 times higher in unvaccinated as compared to vaccinated adults. And the Moderna primary vaccine serieshas been used to vaccinate about 37% of those fully vaccinated, and protectionwith this vaccine declines against infection over time and during the Delta period. On the other hand, there have been minimalto no declines in vaccine effectiveness against hospitalization in younger adultsand mild declines observed in some studies, in some study platforms, among older adults.Approximately 8% of fully vaccinatedpeople received the Janssen COVID vaccine. This vaccine shows lowerVE compared to mRNA vaccines, however most platforms show persistent vaccineeffectiveness over time against infection and hospitalization even among olderadults who receive this vaccine. Next slide. And now, we’ll review theevidence for benefits and harms of the Modern and Janssen COVID boosters. Next slide. So, I know this slide is busy, butbear with me as I walk through it. So, the Moderna’s data for immunogenicity ofa 50-microgram booster, so that’s important to know that that’s a half doseas compared to the primary series. So, for this boost, sorry, thisbooster, following their primary series, the evidence comes from a study of149 subjects, and a larger group with immunogenicity data following theprimary series was available as a comparison. So, at 28 days following the booster dose,the neutralizing antibody titers were about 1.8 times those in the comparisongroup who just received the primary series. Thus, meeting the prespecified endpointfor noninferiority of this comparison. So, it’s important to note that noclinical outcomes were assessed.So, no actual outcomes againstsymptomatic disease were assessed. And that participants were not randomized tothe intervention or comparison group, and therefore, the evidence tied to assessprevention of symptomatic COVID was type four. Or, in other words, very low quality. Sorry, very low certainty. There was no data available to assessthe prevention of hospitalization, death, or transmission of SARS-CoV-2. With respect to possible harms, noserious adverse events were attributed to Moderna booster doses in the 171subjects assessed at the 50-microgram dose. The proportion with any serious adverseevent was balanced between intervention or booster dose and comparison [inaudible]. In terms of reactogenicity at thegrade three level, or in other words, early reaction to the vaccine that mightinterfere daily life in the seven days after receiving the vaccine, 10.8%of the booster group experienced such a reaction compared to 19.7% ofthe primary series comparison group. The certainty for both outcomes were judgedas evidence type four or low certainty. Next slide. Now, to summarize the evidencefor grade of the Janssen booster.So, the evidence for use of the Janssenbooster dose was primarily generated from a clinical trail where subjects wererandomized to receive either two doses of Janssen vaccine 56 days apart or a placebo. Wherever possible, we tried to compare theeffects of the booster dose administered to approximately 7,400 participants toa primary dose administered to a little over 19,000 participants in the initial clinical trial. The Janssen COVID-19 booster dose is, appearsto be more effective at preventing symptomatic, lab-confirmed COVID than the primary dose alone. However, because the participants werenot randomized to the intervention and comparison groups and results were comparedacross two separate studies that differed in both time and geography, the evidence wastype four or low certainty in the estimate. The Janssen booster dose may bemore effective than the primary dose at preventing hospitalizations and deaths due toCOVID, but because of concerns with study design and indirect comparison, and imprecisionresulting in small numbers of outcomes, both of these outcomes wereassessed to be type four evidence. There was no data to assessthe prevention of transmission.For serious adverse events, over 8,000 participants received the boosterdose were compared to placebo recipients. The proportion with any seriousadverse events were balanced between the booster and placebo arms. However, three serious adverseevents were attributed to Janssen COVID booster doseby the study investigators. Those were facial paresis, pulmonaryembolism, and cerebrovascular accident. With respect to reactogenicity, theproportion with a grade three reaction, remember those are ones thatinterfere with daily life, following a booster was similar to or less thanthe primary dose because of lost follow up, short duration of follow up, andindirect comparison and imprecision, meaning the evidence was type four or lowcertainty for both arm outcomes assessed. Next slide. So, large scale and rigorous post authorizationsafety surveillance has identified safety issues that may be too rare to be seenin standard clinical trials. Myocarditis and pericarditis have been observedfollowing Moderna COVID vaccine primary series. This has been noted and included in theemergency use authorization fact sheet available to clinicians and patientsreceiving the vaccine. The risk is noted particularly withinseven days following the second dose and is highest among males under 40. Although most cases resolve, the longterm sequelae are not fully understood.The highest reporting rate is in18-24-year-old males in the zero to seven days post dose two, andthat’s been reported as 39 cases for every million doses administered. Thrombosis with thrombocytopeniasyndrome, also known as TTS, has been identified followingJanssen primary vaccination. TTS involves blood clotswith low levels of platelets and has been reported highestin females age 18 to 49. The highest reporting rate observed thus faris in 30 to 39-year-old females in the zero to 21 days post the vaccine dose and reportedas ten cases per one million doses administered. And the third safety signal notedthus far is Guillan Barre syndrome or GBS has been identified following Janssen. The unadjusted reporting rate in the one to42 days following vaccination has been noted as 20 cases per one million doses administered. And sorry 16 cases per onemillion doses administered. And please note that all these reportingrates cited here will include some level of background incidence, and not allcases may be attributed to vaccination. Next slide.So, heterologous boosting, which I mentionedearlier, also known as mix and match, could provide important immunebenefits as well as enhanced feasibility and implementation of the booster dose program. The National Institute of Health sponsoredstudy showed that use of Moderna, Janssen, and Pfizer BioNTech COVID vaccine asbooster led to a strong serologic response in groups primed by all three of those vaccines. And for a given primary COVID-19 vaccine,heterologous boosts elicited similar or even higher serologic response as compared totheir respective homologous booster responses. mRNA vaccines resulted in higher antibodytiters in the first 28 days after boosting. And although the study arms were eachof them were small, containing about 49 to 53 participants, no safetyconcerns were identified in the over 400 study participants involved.Next slide. Now, let’s look at the feasibilityimplementation with regard to booster doses. Next slide. From August 13th to September 23rd, approximately three million additional doseshad been administered under the recommendation for use in immunocompromised people. So, following the Pfizer booster doserecommendation on September 23rd, the total number of booster or additional doseshas increased to approximately 10.9 million. The majority of those booster doses hasbeen administered in people 65 and older. Next slide. So, this is a figure of the number of people who completed their primaryvaccination regime over time. The Pfizer vaccine recipients in grey,Moderna in orange, and Janssen in blue. Next. And for all three of these vaccines, most people who completed the primary vaccineregime did so more than six months ago. Next slide. And here’s a detailed breakdown of the number of people either six monthspost their mRNA primary series or two months post their initial Janssen dose. For Janssen, that’s about 12.9 million people,and for Moderna, almost 18 million people over the age of 65 as well as 21million people, younger people, a portion of whom may be recommended as a result of the ACIP booster doserecommendations last week.Next. So, in summary, next. The ACIP work group maintainedthat the top priority should be to continue vaccination ofunvaccinated individuals. And that the goals of a booster programshould be the prevention of severe disease, including hospitalization and death. However, the other considerations areimportant, such as maintaining the workforce and healthcare capacity,prevention of transmission, as well as considering individualbenefit and risk. And of course, we know that the balanceof benefits and risks does vary by age.Sorry. Previous slide. So, adults 65 years of age and older havethe clearest benefit risk when thinking about boosters, and for Moderna, the benefitsare incrementally smaller with decreasing age. Given the high effectivenessmaintained for the primary series. Also, myocarditis risk is higherin young adults, especially males. For Janssen, the benefits may be smalleracross age groups compared with mRNA vaccine. And it should be noted that the TTSrisk is higher among young females.Next slide. So, for people who’ve received ModernaCOVID-19 vaccine as a primary series, the work group supports the use ofa single booster dose at a minimum of six months following the primary series incertain populations, those that are consistent with the CDC recommendedpopulations for Pfizer booster. And for people who received the JanssenCOVID-19 vaccine as a primary vaccination, the work group supported use of asingle booster dose at a minimum of two months following the initial dosein all people 18 years of age and older. And a single dose of Janssen wasnoted by the work group resulted in a lower vaccine effectiveness in antibodylevels compared to mRNA vaccine primary series.And the data demonstratedthat a single does of Janssen or mRNA vaccine boosts immuneresponse in these individuals. Next slide. I’d like to thank the many peoplewho made this presentation possible. Next slide. And with that, I would like to handthe microphone over to Dr. Sujan Reddy. >> Thanks, Dr. Dooling. You can go to the next slide. We’re reviewing the updates forour interim clinical considerations for the vaccine boosters.I wanted to start off with telling you thebottom line is, and these are the four points that I think I’d like you to take away here. The first part is that the indication forand the timing of booster doses depend on a primary series that was administered. So, you’ll hear me say the phrases like ifthe person received mRNA primary series, then you should do this. So, which people get the boosterand when they get it will depend on what the primary series is. The second point I’d like to make iswhat Dr. Dooling had just mentioned that the booster product can be thesame or different than a primary series.So, any FDA approved or authorized COVID-19vaccine can be used for the booster dose, regardless of the vaccine thatwas used for the primary series. So, in other words, you can use the samevaccine product for the booster dose, or you can do a mix and match with booster dose. The third point which I saw a lot of questionsabout was if you use the booster dose, the Moderna booster dose, the doseis half of the primary series.So, as a reminder, the primary and additionaldose for Moderna is 0.5 mL or 100 micrograms. Whereas the booster dose isonly 50 micrograms and 0.25 mL. Lastly, I’ll spend some time talking aboutspecial considerations for moderately and severely immunocompromised people, asI know there’s some questions about that. Next slide. So, let’s start with people who completed theirprimary vaccine series with an mRNA product, either Pfizer BioNTech or Moderna. These categories have not changedsince the Pfizer recommendations came out a couple weeks ago, and now theyjust apply for both mRNA products. The following groups who received mRNA primaryseries should receive a single mRNA COVID-19 vaccine booster at least six monthsafter completion of their primary series. So, people that are over the age of 65,people over the age of 18 who reside in long term care settings, andpeople aged 50 to 60, sorry, 50 to 64 with certain underlyingmedical conditions that put them at risk for severe disease. The following groups who received mRNA primaryseries may receive a single COVID-19 booster shot at least six months aftercompletion of their primary series. This is based off of theindividual risks and benefits.So, people at age 18 to 49 withcertain medical conditions. Now, note these certain medicalconditions do include pregnant people. I know that was a question I had. So, people that are pregnant may receive theCOVID-19 booster as well as people that are 18 to 64 who are at increased risk ofSARS-CoV-2 exposure and transmission because of their occupationalor institutional setting. Now, if you’re in one of these groups,the booster dose should be administered at least six months at the completion ofthe mRNA series, and as I noted before, any FDA approved authorized product, any ofthe three, can be used as a booster dose, regardless of the vaccinereceived in the primary series.So, even if you got an mRNA primary series,you can get either that same mRNA product, a different mRNA product,or the Janssen booster. Next slide. As a reminder, for the categoryof people who may, quote unquote, may receive a COVID-19 booster, werecommend risk benefit assessment considering these factors. Does a person have an increasedrisk for SARS-CoV-2 infection? This might come from increased risk to exposure from their occupational orinstitutional exposures. It also might be their risk relatedto other factors since their time from completion of their initial primary series. If the individual were to be infected, they may want to consider whatimpact the virus could have on themselves as well as those around them. Individuals with underlying medical conditionsare at increased risk for severe infection, but also importantly, people may wantto consider their person circumstances.So, such as if they live or are caring forpeople who are at risk for severe disease. They may even want to consider nonsevereinfections and the consequences they may have on their ability to do other obligationssuch as work because if they get infected. The person should also considerthe benefits of the booster shot. The booster, as Dr. Dooling mentioned, theboosters may reduce their risk for infections, including the risk for severe infection. And lastly, a person should consider the potential risks,including the common risks such as the transient and local systemic symptomsthat come after a vaccination, but also the rare risk of booster shots.Next dose. Sorry, next slide. People who received an mRNA or Janssen primarydose, the indications for boosters are simpler. All people age over 18 whoreceived a single dose of Janssen primary series should receive asingle COVID-19 booster dose at least two months after completing their primary series. And again, they can receive any of thethree vaccine products as long as it is over two months from their primary dose. I should, as there’s some questions in the chat. The risk groups that I went overbefore only apply to the mRNA, the people that got an mRNA primary series. So, anyone over the age of 18 who got a Janssendose is at least two months from their primary, from their Janssen dose iseligible for a booster shot. Next slide. I wanted to lay out where we stand in termsof the dosing, number of doses recommended, and the age recommendations from theprimary series and the booster dose.So, for the Pfizer BioNTech recommendations,these recommendations are unchanged for the primary and booster doses. The dose of the Pfizer primaryand booster doses are the same. I would also note that even though adolescentsage 12 to 17 should receive a primary series of Pfizer, they are not eligiblefor a booster dose at this time. For the Moderna vaccine, you can alsosee that the booster dose is half of the primary dose, the 0.25 mL.Excuse me. As for the Janssen, as I mentioned, peopleover the age of 18 who receive Janssen would, should be getting a booster dose atleast two months from their initial. The dose of the booster, the Janssen boosterdose is the same as the primary series. Now, when heterologous booster doses or mixand match booster doses are administered, the booster dose eligibilitycriteria in the interval for receiving the booster doseare those that for the vaccine that was received for the primary vaccination. Next slide. Now, let’s talk a little bit moreabout heterologous booster doses, known as mix and match booster doses. Heterologous dosing may be considered onlyfor the booster dose, so all primary doses and additional doses shouldutilize the same vaccine product. And as I’ll describe later, just as areminder, additional doses refer to those that are indicated for moderatelyand severely immunocompromised people who had received two doses of an mRNA product.I also just mentioned that theinterval between the booster dose and the primary series dose should follow theinterval recommended by the primary series. So, people who receive Janssen primarydose can receive an mRNA booster dose at least two months after the Janssen dose. A common question may be whichproduct should your patient use. As Dr. Dooling described, thereis evidence supporting the use of either homologous or heterologousbooster dosing. People may consider this electionof a booster dose just simply by based off of what’s available. They may also want to talk to theirproviders about the risk profiles of different vaccine boosters,including rare events. Next slide. So, the previous presenters talkedabout this, but just to remind, the potential risks associated with theCOVID-19 vaccine boosters are based off of the rare events that wereobserved after primary vaccination.So, for the Janssen vaccine, thrombosiswith thrombocytopenia syndrome or TTS is a severe adverse event. The highest risk has beenobserved in women age 18 to 49, so women in this age category should becounseled about this risk and made aware of the options to receive an mRNA booster dose. Other rare risks include Guillain Barre syndrome which is highest risk observedin men age 50 to 64. For the mRNA vaccines, the Pfizerand Modern vaccines, myocarditis and pericarditis has beenobserved after the vaccine, and the highest risk observedin men age 12 to 30.Next slide. So, we’ve received many questionsabout moderately and severely immunocompromised people, so I wanted to review a recommendationfor this population. Next slide. So, just to review a few definitions. We use the term “additional dose” to referto a subsequent vaccine dose in people who likely did not mount a protective immuneresponse after their primary vaccination in order to optimize theirvaccine induced protection. In other words, their initialresponse was likely insufficient. A booster dose is a subsequent dose administeredwhen the initial sufficient immune response to the primary series islikely to have waned over time. So, in other words, the initial response wasfine, but over time, the response has decreased. We worry about people who areimmunocompromised fall into that first category where their initial response to the vaccine isinsufficient, so they need an additional dose. Next slide. So, our recommendation for moderately and severelyimmunocompromised people age 12 or older for the Pfizer or over 18 for Moderna who received an mRNA COVID-19 vaccine primaryseries should receive an additional mRNA vaccine dose at least 28 days after their second dose. I would note that even though we areallowing mix and match for booster doses, the primary series and additional dosesshould be the same as the initial dose.I would also mention that the recommendationdoes not apply to immunocompromised people who receive Janssen as a primary series,as you’ll see in a couple of slides. Next slide, please. So, what do we mean by moderately andseverely immunocompromised people? I know this is a challenge to assess, but oneway of categorizing it is thinking of people who had a solid organ transplant orequivalent level of immunosuppression.Here, I provide a list of immunocompromisedconditions that may warrant additional doses, such as people who have, that arereceiving treatment for a solid tumor or hematological illness, people that are receiving CAR-T-celltherapy or stem cell transplant. People with severe primaryimmunodeficiencies or advanced HIV. And I know there’s a long list ofimmunosuppressants that I’ve listed here, and consulting with their provider may helpdecide if an additional dose is indicated. Next slide, please. So, I wanted to summarize how to approachvaccination in this immunosuppressed population. If the person received an mRNA primary series,they should get an mRNA additional dose at least 28 days after their second dose. Note, if that dose is a Moderna dose, they should get a full doseof Moderna which is a 0.5 mL. Then, six months later, aftertheir additional dose, they can receive a COVID-19 vaccinebooster, and that could be any of those three authorized products. And again, if Moderna is usedfor a booster dose, that should, they should receive the halfdose as a booster dose.And I would also note, if Pfizer is usedfor any of these doses, it’s the same doses as for the primary, additional,and the booster dose. Now, if the person received a Janssenprimary series, they should receive any of the COVID-19 vaccine boosters at leasttwo months after the initial Janssen dose. And again, if Moderna is used in this situation, the Moderna booster dose should beused which is the half dose, 0.25 mL. Next slide, please.Now, I wanted to move on to a couple of additional considerationsfor the booster regime. Next slide. Briefly, the definition of fully vaccinated hasnot changed with these booster recommendations. People who completed a primary series areconsidered fully vaccinated at least two weeks after their completion of their primary series which involves a two dose mRNA vaccineseries or a single dose of Janssen. So, even if people are recommended toget an additional dose or recommended to get a booster dose, as long asthey received that primary series, they’re considered fully vaccinated.Next slide, please. Given that we’re ramping up influenzavaccination, we wanted to reiterate the points about co-administration with other vaccines. The COVID-19 vaccine booster is similar tothe primary and additional doses may be given with other vaccines, regardless of timing. This includes all three ofthe authorized vaccines. This is also includes simultaneousadministration of COVID-19 vaccines and other vaccines on the same day. Next slide. I think I’m going to actually skip this slide. Just know that you know, the clinicalconsiderations document that I’ll link in the next slide have a lotof other recommendations, and we did update a few othersthat I mentioned here. I’d also mention that document is verylong, and so we are updating a lot of our provider-facing documents that give nice,clear summaries that providers can utilize. So, look for those in thenext couple of days as well. I think that’s all from my slides, sothank you, and I think we can take Q and A according to the moderator.>> Thank you very much, presenters. I appreciate your providing ouraudience with this timely information. We will now go into our Q and A session. We would also like to welcome Captain TomShimabukuro who is on the Vaccine Taskforce as part of CDC’s COVID-19response for joining us for the Q and A session along with the speakers. Please remember to ask a question usingZoom, click the Q and A button at the bottom of your screen and type your question.So, our first question for the presenters iswhat recommendations do you have for boosters for people who are now back in the United Stateswho may have gotten the Astra Zeneca vaccine or the Sinovac vaccine while abroad? >> Thanks. I can take that question. So, for people that received an FDAauthorized series, either the homologous series or a mixed series, we would recommend abooster according to what we just discussed. Now, people that received other vaccinesthat are emergency use listed by the WHO such as the Astra Zeneca vaccine, we actually, wedo consider those people fully vaccinated, but at the moment, we don’t have boosterrecommendations for that population. We continue to work with our internationalcolleagues to try to figure that out. But at the moment, we haveno recommendation for that. >> Thank you very much. Our next question is regardingthe long-term care setting aspect of consideration when discussing boosters. You’ve had multiple questions around this. Essentially, it boils down to shouldwe consider other settings similar to long term care settings such as correctionalfacilities or college students dwelling together in dorms as being at an increasedrisk for SARS-CoV-2 infection and thereby being possiblecandidates for boosters? >> Yeah.I can take this as well. And so, this falls into thecategory of, well, first, I would say if they received a Janssen doseand they’re over the age of 18 and it’s been at least two months, then theyshould receive a booster dose. Now, if they received an mRNA primary seriesand then six months later, then they may fall into that may receive a booster shot. And I would say there’s a CDC website that sayswho’s eligible for a COVID vaccine booster.And it goes into this a little bit more detail. But basically, it’s based offof where you work or reside, and it does include healthcare settings,correctional facilities, homeless shelters, where they might be at an increased risk ofbeing exposed to COVID-19 and could be spreading in that workplace or where they reside. So, I’d probably refer people to that, andthat does have a list of occupational settings and other institutional settingsthat might be helpful for people that are asked those types of questions. >> Thank you very much. Our next question is regarding v-safe, and thequestion asks do patients need to sign up again with v-safe when receiving boosters? >> Hi.This is Dr. Hause. Patients do not need to registeragain for v-safe. If they go ahead and go to the v-safehomepage and enter their information, they’ll be sent a hyperlink through textthat will link them to their profile. >> Thank you very much. Our next question is regardingthe difference in concentration or dose between the additional doseof Moderna versus the booster dose. And the questions essentiallyare inquiring about elaborating on the immune response difference betweenthe additional dose versus the booster dose, considering that they are not the same. >> This is Dr. Kathleen Dooling. I can take that one. So, we have a number of studiesto help us sort out this question. You’re absolutely right.Primary series for Moderna isgiven at 100 microgram dose, and now we authorize boosterdose is a 50-microgram dose. And it’s the same formulation. It’s just half the volume that should begiven to the patient in the booster dose. So, in small studies, Moderna tested boththe 50 microgram as well as 100 microgram as a booster dose, and it turnsout that they provided fairly similar amount of serologic boosting to people whopreviously received the primary series. In terms of the mix and match studies doneby NIH, a number of the listeners here noted that that was at 100 microgramlevel which is true. So, that would be, you know, different fromwhat has been authorized for a booster at the 50-microgram level, but I thinkthose studies done early on by Moderna that showed that, you know, 50 or 100micrograms provide an adequate boost is, it’s a good footing for us to move forwardwith the authorized 50 microgram booster dose.>> Thank you. Our next question asks for a person whoreceived a full course of an mRNA vaccine, is there ever a reason for them to receivethe J and J vaccine as their booster? >> So, this is. >> Hi. This is Dr. – Go ahead. >> Yeah. Sure. I think they can. And to be clear, you know, let’s saythey’d received the two dose mRNA series, and it’s been over six months. Yes, they may receive the Janssendose, or they may receive any of the mRNA products at that time. We don’t necessary state a preferenceabout which they should utilize, and I think they should consider those factorsthat we talked about before, what’s available and potential rare side effects,along with some of the details that Dr. Dooling just mentionedabout some of the mRNA vaccines. They can receive the Janssen dose equally.>> Thank you. Our next question asks will those whoreceived an additional mRNA dose based on perhaps their immune status, arethey eligible for a booster six months after that additional dose aswell, and how about annually? >> This is Sujan Reddy again. So, if it’s immunocompromised person whoreceived two doses of an mRNA vaccine, they can get a third additional dose 28 dayslater of an mRNA vaccine, and then six months after that third additional dose, thatthird mRNA dose, six months later, they can receive any boosterdose of the three vaccines.Now, after that period of time, I thinkobviously time will tell, and we will be ready to update our guidance as more data comes out. But at the moment, they canreceive up to those four doses. >> Thank you very much. And in the remaining time we have, wehave time for really one last question, and this is a question that we’veseen a lot in the Q and A box. And it might be good for youto elaborate or reiterate some of the things the three presenters talked about. And that’s essentially are there any changesin timing and duration in how long to wait between first, second, booster, etc.Whenmixing and matching the various vaccines? >> So, I can try to take a stab, answer that. So, just to be clear, if we’re mixing andmatching, we’re only recommending mixing and matching for the booster dose. So, if it’s a primary series or even thatadditional dose for immunocompromised people, they should stay with the sameseries, same vaccine product that they used as an initial dose. And then, the recommendation for thebooster dose doesn’t necessarily change if you used a homologous dose or a mix and matchdose, if I understood the question correctly.>> Thank you very much. >> This is Dr. Dooling. >> Yes, Dr. Dooling. >> If I can add to that. I would say that the timing ofthe booster dose really depends on what you received as your primary dose. If you received a Janssen primary dose, thenthose people are eligible for their booster at a minimum of two months after thatdose for anybody who’s 18 and older. If you received an mRNA vaccine as yourprimary series, those folks are eligible for a booster dose at a minimum of sixmonths after the second dose in that series. And with the recommendations for who should and who may receive a dosethat we mentioned earlier. >> Thank you very much. That is very helpful. I want to thank everyone for joining us todaywith a special thanks to our presenters. Today’s COCA Call will be available ondemand a few hours after the live call. You can find the video recording of today’sCOCA call at emergency.cdc.gov/coca. Join us for our next COCA call on Thursday,November 4 from 2:00 PM to 3:00 PM Eastern where the topic will be pediatricCOVID-19 vaccines, CDC’s recommendations for COVID-19 primary series inchildren five to 11 years old.However, please note that this COCA call iscontingent on upcoming FDA and CDC meetings. As such, it is subject to change. We will keep you posted. Continue to visit emergency.cdc.gov/coca toget more details about upcoming COCA Calls, as we intend to host more COCAcalls to keep you informed of the latest guidance and updates on COVID-19. Please share these call announcementswith your clinical colleagues. You can also sign up to receiveweekly COVID-19 Science Updates by visiting this link onthis webpage, on this slide.Next slide. COCA Call announcements for upcoming COCA Callsand other COCA products are sent via email. In addition to visiting our webpage,please remember to subscribe to COCA to receive notifications about upcoming COCAcalls or other COCA products and services. Be sure to subscribe to receive notificationsby going to emergency.cdc.gov/coca. Again, that’s emergency.cdc.gov/coca. We invite you to join the COCA email list by visiting the COCA webpageat emergency.cdc.gov/coca. Click on the Get Email Updates and enteryour email address where indicated.To stay connected to the latest news fromCOCA, be sure to like and follow us on Facebook at facebook.com/cdcclinicianoutreachandcommunicationactivity. Again, thank you for joining us fortoday’s COCA Call, and have a great day..
