37 - Viral Vaccines

vaccine

biological preparation that provides active acquired immunity

• exposes immune system to antigens, creating memory and protection against future infections

• different vaccines types vary in strength, safety, and duration of immunity

active vs passive immunizations

• active → dead, live attenuated, purified, recombinant or synthetic antigens

  • used as prophylactic measure

  • lag time present

  • long-term immunity

  • may need boosters

• passive → preformed antibodies

  • used as a therapy

  • no lag time

  • short-term immunity

types of vaccines

• live attenuated — oral polio vaccine, measles, mumps and rubella (MMR), varicella, rotavirus, yellow fever

  • advantages → strong protective immune response, long-term immunity

  • disadvantages → safety concerns, adverse reactions, reversion to virulence, less stable

• inactivated / killed → hep A, polio virus (salk), influenza, rabies

  • advantages → strong humoral immune response, no reversion to virulence

  • disadvantages → weak immune response, multiple booster required, no local immunity, higher cost of production, insufficient activation of virulent virus may cause disease

  • toxoid, subunit, conjugate vaccines

• recombinant — hep B, HPV

new generation vaccines

• first generation vaccines — whole organism (killed or live attenuated)

• second generation vaccines — subunit, conjugate, toxoid, and recombinant protein antigen vaccines

• third generation vaccines — DNA vaccines

• combination vaccines — MMR, MMRV, hep A and B

• edible vaccines — rabies

• heterologous vaccines (viral vectored) — vaccinia, Ebola, COVID-19

• mRNA vaccines — COVID-19

routes of vaccine administration

• oral → subine oral polio vaccine, rotavirus and adenovirus vaccines

• intramuscular route → rabies, hep A and hep B, varicella, HPV, inactivated influenza, COVID-19

• subcutaneous → MMR and yellow fever

• scarification → smallpox

• intranasal → live attenuated influenza

smallpox vaccine

first disease eradicated by vaccine; live virus vaccinia

• variolation → inoculation of susceptible population with virulent smallpox pus

• insufflation → nasal insufflation of powdered smallpox scabs

• Edward Jenner’s cowpox vaccine → live vaccine with one antigenic type and no animal reservoirs

• Dryvax smallpox vaccine → lyophilized live vaccinia virus grown on calf skin

• ACAM2000 → vaccinia virus cultured in calf kidney epithelial cells

• IMVAMUNE → live non-replicating MVA-BN

monkeypox vaccine

virulent Orthopoxvirus endemic in some regions of Central Africa; live virus vaccine

• zoonotic infection, with human-to-human transmission

• symptoms — fever, headache, prostration, pustular rash covering entire body

• vaccines — smallpox vaccine prevents monkeypox

  • JYNNEOS → smallpox and monkeypox live nonreplicating vaccine used for preexposure prophylaxis

polio vaccines

• Sabin → live, oral

  • not used in US

  • produces local infection in gut

  • production of mucosal immune response (sIgA)

  • immunocompromised individuals at risk of developing vaccine-related polio

• Salk → inactivated, parental

  • produces only an IgG response, which provides excellent protection against development of poliomyelitis

  • facilitates development of sIgA response to polio

MMR and MMRV vaccines

measles, mumps, rubella, and varicella

• live attenuated viruses

• children → 2 doses

  • first dose at 12-15 months

  • second dose at 4-6 years

  • children 6-11 months should receive one dose of MMR at least two weeks before travel

• adults → 2 doses recommended for adults at high risk

  • international travelers, college and post-high school students, healthcare personnel

varicella vaccine

varicella (chickenpox) is a febrile rash illness resulting from primary infection with VZV

• transmission occurs from person-to-person by direct contact with either varicella or herpes zoster lesions by airborne spread from respiratory secretions or lesions of persons with chickenpox

• varivax → live attenuated single-antigen varicella vaccine

• MMRV → combination containing measles, mummps, rubella, varicella

  • thermolabile → must be kept cold

zoster vaccine

VZV remains in latent stage in human nerve tissue and reactivates in approximately one in three persons during their lifetime, resulting in herpes zoster (shingles)

• decline or relative absence of cell-mediated immunity is considered an important factor in development of herpes zoster

• zostavax → live vaccine

  • administered as one-time subcutaneous injection

• shingrix → equivalent to 14 doses of pediatric live chickenpox vaccine

  • recommended for adults 50 years and older, 2-6 months apart

  • can be used as therapeutic vaccine

rotavirus vaccine

rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide

• RotaTeq → live, oral human-bovine reassortant rotavirus vaccine

• Rotarix → live vaccine that contains attenuated monovalent G1, P human rotavirus strain

adenovirus vaccine

vaccines developed for serotypes 4 and 7 are available only for preventing ARD among military recruits

• live virus vaccine

• febrile respiratory illness (FRI) cases decreased since vaccine was reintroduced

yellow fever vaccine

live attenuated 17D strain (YF-Vax)

• highly effective vaccine administered to residents in the tropics and travelers to endemic areas

• single dose induces protective immunity

• booster every 10 years for residents in endemic areas

dengue fever vaccine

dengvaxia vaccine is a live attenuated yellow fever (17D)-based tetravalent recombinant vaccine

• available in the US for children 9-16 years with confirmed evidence of prior dengue and living in dengue-endemic areas

• protects against all. four dengue virus types

• 3 doses, administered subcutaneously 6 months apart

hepatitis B vaccine

two single-antigen recombinant hepatitis B vaccines available

• Recombivax HB → 5-40µg of HBsAG protein/mL

• Engerix-B → 20µg/mL

• routinely administered in three-dose series at 0, 1, and 6 months

• Engerix-B also licensed for four-dose series administered at 0, 1, 2, and 12 months

hepatitis A and B vaccine

Twinrix combined hepatitis A and B vaccine for >18 years of age

• Comvax → recombinant HBsAg and Haemophilius influenza type B (Hib) polyribosylribitol phosphate conjugated vaccine

• Pediarix → recombinant HBsAg, diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), and inactivated poliovirus (IPV)

• combination vaccines not administered to infants younger than 6 weeks, with exception to Twinrix

HPV vaccines

L1 major capsid protein assembled into virus-like particles

• Cervarix (2vHPV) → bivalent HPV-16 and -18

• Gardasil (4vHPV) → tetravalent formulation of HPV-6, -11, -16, and -18

• Gardasil 9 (9vHPV) → VLPs 6, 11, 16, 18, 31, 33, 45, 52, and 58

• HPV vaccine recommended for preteen girls and boys at age of 11 or 12 years

• 2vHPV, 4vHPV, and 9vHPV administered in three-dose schedule

  • second dose administered at least 1 to 2 months after first dose

  • third dose administered at least 6 months after first dose

  • if vaccine schedule is interrupted, vaccination series does not need to be restarted

influenza vaccine

annual influenza vaccination recommended for all persons 6 months of age and older

• both inactivated and live attenuated available

• FluMist → live attenuated influenza vaccine

  • administered intranasally and approved for healthy persons age 2-49 years

  • not recommended for immunocompromised or pregnant women

• inactivated virus → injection in persons 6 months and older

• both live and inactivated are tri- or quadrivalent vaccines

  • contain three or four influenza virus strains → two type A influenza (H3N2 and H1N1) and influenza B (single or two)

• vaccine strains selected each year to represent strains judged most likely to circulate during influenza season

rabies vaccine

• preexposure immunization:

  • human diploid cell cultures vaccine (HDCV) at 0 and 7 days (IM)

  • purified chick embryo cell (PCEC) at 0 and 7 days (IM)

• postexposure immunization:

  • not previously vaccinated → rabies immunoglobulin (RIG) single dose at bite site, IM HDCV or PCEC on days 0, 3, 7, 14 (IM)

  • previously vaccinated → HDCV or PCEC on days 0 and 3 (IM)

• raboral V-RG → vaccination of domestic animals and control of wild animals

  • recombinant vaccinia virus vaccine expressing G protein

inactivated SARS-CoV-2 vaccine

two-dose vaccine administered 28 days apart

• Covaxin

• Sinovac

Ebola vaccine

• cAd3ZEBOV → chimpanzee adenovirus 3 engineered to express glycoproteins from Zaire EBOV and Sudan EBOV

• VSVEBOV → vesicular stomatitis virus engineered to express Zaire EBOV glycoprotein

vaccine technology

• mRNA vaccines → deliver mRNA for cells to make antigen and elicit immune response

• viral vector vaccines → use harmless virus to deliver antigen

• DNA vaccines → experimental